Breast implant with regionalized analyte sensors responsive to external power source

ABSTRACT

Breast implants including sensor modules and related methods are described herein. Breast implants include those with: a shell configured to be substantially filled with a viscous material; a plurality of projections extending from an external surface of the shell, the projections forming a plurality of compartments adjacent to the external surface of the shell; at least one fluid-permeable cover attached to the projections, the cover completely enveloping the shell and the plurality of projections; and a plurality of sensor modules attached to the shell and positioned at a distance from each other, each of the sensor modules oriented to detect one or more analytes in a fluid within one of the plurality of compartments, wherein each of the plurality of sensor modules includes a unique identifier and is configured to utilize energy transmitted from an external source.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is related to the following listedapplication(s) (the “Related Applications”). All subject matter of theRelated Applications and of any and all parent, grandparent,great-grandparent, etc. applications of the Related Applications, isincorporated herein by reference to the extent such subject matter isnot inconsistent herewith.

RELATED APPLICATIONS

United States patent application No. To Be Assigned [attorney docketnumber 0411-002-002-000000], entitled BREAST IMPLANT WITH ANALYTESENSORS AND INTERNAL POWER SOURCE, naming Edward S. Boyden, Gregory J.Della Rocca, Paul Duesterhoft, Daniel Hawkins, Roderick A. Hyde, RobertLanger, Eric C. Leuthardt, Terence Myckatyn, Parag Jitendra Parikh,Dennis J. Rivet, Joshua S. Shimony, Michael A. Smith, Elizabeth A.Sweeney and Clarence T. Tegreene as inventors, filed 13 Jun. 2012.

United States patent application No. To Be Assigned [attorney docketnumber 0411-002-003-000000], entitled BREAST IMPLANT WITH ANALYTESENSORS RESPONSIVE TO EXTERNAL POWER SOURCE, naming Edward S. Boyden,Gregory J. Della Rocca, Paul Duesterhoft, Daniel Hawkins, Roderick A.Hyde, Robert Langer, Eric C. Leuthardt, Terence Myckatyn, Parag JitendraParikh, Dennis J. Rivet, Joshua S. Shimony, Michael A. Smith, ElizabethA. Sweeney and Clarence T. Tegreene as inventors, filed 13 Jun. 2012.

United States patent application No. To Be Assigned [attorney docketnumber 0411-002-004-000000], entitled BREAST IMPLANT WITH COVERING,ANALYTE SENSORS AND INTERNAL POWER SOURCE, naming Edward S. Boyden,Gregory J. Della Rocca, Paul Duesterhoft, Daniel Hawkins, Roderick A.Hyde, Robert Langer, Eric C. Leuthardt, Terence Myckatyn, Parag JitendraParikh, Dennis J. Rivet, Joshua S. Shimony, Michael A. Smith, ElizabethA. Sweeney and Clarence T. Tegreene as inventors, filed 13 Jun. 2012.

United States patent application No. To Be Assigned [attorney docketnumber 0411-002-005-000000], entitled BREAST IMPLANT WITH COVERING ANDANALYTE SENSORS RESPONSIVE TO EXTERNAL POWER SOURCE, naming Edward S.Boyden, Gregory J. Della Rocca, Paul Duesterhoft, Daniel Hawkins,Roderick A. Hyde, Robert Langer, Eric C. Leuthardt, Terence Myckatyn,Parag Jitendra Parikh, Dennis J. Rivet, Joshua S. Shimony, Michael A.Smith, Elizabeth A. Sweeney and Clarence T. Tegreene as inventors, filed13 Jun. 2012.

United States patent application No. To Be Assigned [attorney docketnumber 0411-002-006-000000], entitled BREAST IMPLANT WITH REGIONALIZEDANALYTE SENSORS AND INTERNAL POWER SOURCE, naming Edward S. Boyden,Gregory J. Della Rocca, Paul Duesterhoft, Daniel Hawkins, Roderick A.Hyde, Robert Langer, Eric C. Leuthardt, Terence Myckatyn, Parag JitendraParikh, Dennis J. Rivet, Joshua S. Shimony, Michael A. Smith, ElizabethA. Sweeney and Clarence T. Tegreene as inventors, filed 13 Jun. 2012.

SUMMARY

In some aspects, a breast implant includes but is not limited to: ashell configured to be substantially filled with a viscous material; aplurality of projections extending from an external surface of theshell, the projections forming a plurality of compartments adjacent tothe external surface of the shell; at least one fluid-permeable coverattached to the projections, the cover completely enveloping the shelland the plurality of projections; and a plurality of sensor modulesattached to the shell, each of the sensor modules oriented to detect oneor more analytes in a fluid within one of the plurality of compartments,wherein each of the plurality of sensor modules includes a uniqueidentifier and is configured to utilize energy transmitted from anexternal source. In some aspects, a breast implant includes but is notlimited to: a shell configured to be substantially filled with a viscousmaterial; a plurality of projections extending from an external surfaceof the shell, the projections forming a plurality of compartmentsadjacent to the external surface of the shell; at least onefluid-permeable cover attached to the projections, the cover completelyenveloping the shell and the plurality of projections; a plurality ofsensor modules attached to the shell, each of the sensor modulesoriented to detect one or more analytes in a fluid within one of theplurality of compartments, wherein each of the plurality of sensormodules includes a unique identifier; at least one antenna; an energyharvesting unit attached to the at least one antenna; and at least oneconnection between the energy harvesting unit and each of the pluralityof sensor modules. In some aspects, a breast implant includes but is notlimited to: a shell configured to be substantially filled with a viscousmaterial; a plurality of projections extending from an external surfaceof the shell, the projections forming a plurality of compartmentsadjacent to the external surface of the shell; at least onefluid-permeable cover attached to the projections, the cover completelyenveloping the shell and the plurality of projections; a plurality ofsensor modules attached to the shell, each of the sensor modulesoriented to detect one or more analytes in a fluid within one of theplurality of compartments, wherein each of the plurality of sensormodules includes a unique identifier; at least one optically poweredtransducer configured to harvest optical energy from a source externalto the breast implant; and at least one connector operably connectingthe at least one optically powered transducer and the plurality ofsensor modules. In some aspects, a breast implant includes but is notlimited to: a shell configured to be substantially filled with a viscousmaterial; a plurality of projections extending from an external surfaceof the shell, the projections forming a plurality of compartmentsadjacent to the external surface of the shell; a plurality of sensormodules attached to the shell, each of the sensor modules configured todetect one or more biological analytes arising from biological tissue,the fluid within one of the plurality of compartments; at least oneantenna; an energy harvesting unit attached to the at least one antenna;and at least one connection between the energy harvesting unit and eachof the plurality of sensor modules. In addition to the foregoing, otherdevice and system aspects are described in the claims, drawings, andtext forming a part of the present disclosure.

In one aspect, a method of monitoring information from a breast implantincludes but is not limited to: receiving first information from a firstsensor module attached to a shell of a breast implant within anindividual, wherein the first information includes a first unique sensormodule identifier and sensor data from the first sensor module;receiving second information from a second sensor module attached to theshell of the breast implant within the individual, wherein the secondinformation includes a second unique sensor module identifier and sensordata from the second sensor module; forming an initial record from thefirst information and the second information; calculating deviationlimits regarding the initial record; setting deviation parameters basedon the deviation limits and a predetermined set of standards; saving theinitial record and the deviation parameters in memory in a computingdevice; receiving third information from the first sensor moduleattached to the shell of the breast implant within the individual,wherein the third information includes the first unique sensor moduleidentifier and sensor data from the first sensor module; receivingfourth information from the second sensor module attached to the shellof the breast implant within the individual, wherein the fourthinformation includes the second unique sensor module identifier andsensor data from the second sensor module; updating the initial recordwith the third information and the fourth information; saving theupdated record in memory in the computing device; comparing the updatedrecord to the initial record and to the deviation parameters; andindicating if the updated record is within the deviation parameters ofthe initial record. In one aspect, a method of monitoring informationfrom a breast implant includes but is not limited to: sending a signalfrom a transmission unit attached to one or more sensor modules attachedto a breast implant in vivo, wherein the signal contains informationregarding the detection of one or more biological analytes by the one ormore sensor modules. In one aspect, a method of monitoring informationfrom a breast implant includes but is not limited to: directing, from anex-vivo device, a non-electrical power source to a breast implantin-vivo; sending, from a remote device, a query signal to at least onetransmission unit attached to the breast implant in vivo, the at leastone transmission unit attached to one or more sensor modules configuredto detect biological analytes in fluid from biological tissue;receiving, from a remote device, a response signal from the at least onetransmission unit attached to the breast implant, the response signalincluding information from the one or more sensor modules; processing,in a computing device, the response signal to identify information fromthe one or more sensor modules; and identifying, for each of the one ormore sensor modules, a detection result and a unique identifier. In oneaspect, a method of monitoring information from a breast implantincludes but is not limited to: directing, from an ex-vivo device, anon-electrical power source to a breast implant in vivo; sending asignal from at least one transmission unit attached to the breastimplant in vivo, the signal including information regarding one or moresensor modules configured to detect biological analytes in fluid frombiological tissue, the at least one transmission unit attached to theone or more sensor modules; receiving, at a remote device, the signalfrom the at least one transmission unit attached to the breast implant;processing, in a computing device, the signal to identify informationfrom the one or more sensor modules; and identifying, for each of theone or more sensor modules, a detection result and a unique identifier.In addition to the foregoing, other method aspects are described in theclaims, drawings, and text forming a part of the present disclosure.

In one or more various aspects, related systems include but are notlimited to circuitry and/or programming for effecting theherein-referenced method aspects; the circuitry and/or programming canbe virtually any combination of hardware, software, and/or firmwareconfigured to effect the herein- referenced method aspects dependingupon the design choices of the system designer.

In addition to the foregoing, various other device, method and systemaspects are set forth and described in the teachings such as text (e.g.,claims and detailed description) and drawings of the present disclosure.

The foregoing summary is illustrative only and is not intended to be inany way limiting. In addition to the illustrative aspects, embodiments,and features described above, further aspects, embodiments, and featureswill become apparent by reference to the drawings and the followingdetailed description.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a schematic of a breast implant in vivo.

FIG. 2 is a schematic of a breast implant ex vivo from an external view.

FIG. 3 is a schematic of a breast implant ex vivo in cross-section view.

FIG. 4 is a schematic of a breast implant ex vivo in cross-section view.

FIG. 5 is a schematic of a breast implant ex vivo in cross-section view.

FIG. 6 is a schematic of a breast implant ex vivo in cross-section view.

FIG. 7 is a schematic of a sensor module.

FIG. 8 is a schematic of a breast implant ex vivo in cross-section view.

FIG. 9 is a schematic of a breast implant in vivo in cross-section viewin communication with a remote device.

FIG. 10 is a schematic of a remote device.

FIG. 11 is a schematic of a sensor module.

FIG. 12 is a schematic of a breast implant ex vivo in cross-sectionview.

DETAILED DESCRIPTION

In the following detailed description, reference is made to theaccompanying drawings, which form a part hereof. In the drawings,similar symbols typically identify similar components, unless contextdictates otherwise. The illustrative embodiments described in thedetailed description, drawings, and claims are not meant to be limiting.Other embodiments may be utilized, and other changes may be made,without departing from the spirit or scope of the subject matterpresented herein.

The use of the same symbols in different drawings typically indicatessimilar or identical items.

With reference now to FIG. 1, shown is an example of a breast implant invivo that may serve as a context for introducing one or more devices andprocesses described herein. The breast implants and related systems andmethods described herein can be utilized in breast augmentation (e.g.for cosmetic purposes) as well as in breast reconstruction (e.g. aftermastectomy or lumpectomy). The breast implants and related systems andmethods described herein can be utilized in a low-profile implantdevice, for example configured for use after lumpectomy or in a malepatient. FIG. 1 illustrates a breast implant 140 in vivo within anindividual person's body. FIG. 1 shows a cross-section view through theside of a person, including a cross-section of the individual's ribs 130in the chest wall 122, 120, 124. FIG. 1 depicts a cross-section view ofthe breast implant 140 in situ within a breast 100. The breast implant140 includes a shell 145 configured to be substantially filled with aviscous material. The viscous material can be selected for a combinationof non-toxicity as well as to provide structural support to thesurrounding tissue while maintaining a natural feel. For example, theviscous material can include saline or a silicone gel. The breastimplant 140 includes a fluid-permeable cover 155, the cover completelyenveloping the shell 145. As illustrated in FIG. 1, there is a gap 160between the fluid-permeable cover 155 and the shell 145. A series ofprojections 165 extend from the external surface of the shell 145. Theprojections 165 are located between the sensor modules 150 on thesurface of the shell 145. As illustrated in FIG. 1, the projections 165are positioned on the on the surface of the shell 145 to form acompartment around each of the sensor modules 150. The projections 165form a plurality of compartments adjacent to the external surface of theshell 145 within the gap 160. The series of projections 165 extend fromthe external surface of the shell 145 to the fluid-permeable cover 155and are attached to both the external surface of the shell 145 to asurface of the fluid-permeable cover 155. Some embodiments include acover 155 configured to completely envelop the shell 145 with a uniformgap 160 between the cover 155 and the shell 145, wherein the projections165 are approximately the same height as the width of the gap 160.

The breast implant 140 includes a plurality of sensor modules 150 A, B,C, D, E, F and G. Each of the sensor modules 150 A, B, C, D, E, F and Gis attached to the shell 145 and oriented to detect one or more analytesin a fluid within one of the plurality of compartments adjacent theshell 145. The compartments are configured to allow for fluid flow fromthe adjacent tissue into the compartments through the fluid-permeablecover 155, as illustrated in FIG. 1 by the dotted arrows. The sensormodule 150 located within each compartment is oriented to detectanalytes in the fluid from the adjacent tissue. Each sensor module ispositioned to detect one or more analytes in fluid from tissue in itssurrounding regions. For example, sensor module 150 C is oriented todetect one or more analytes in fluid from tissue in its surroundingregions, identified in FIG. 1 as 112 and 110. Also by way of example,sensor module 150 D is oriented to detect one or more analytes in fluidfrom tissue in its surrounding regions, identified in FIG. 1 as 110 and114. As another example, sensor module 150 E is oriented to detect oneor more analytes in fluid from tissue in its surrounding regions,identified in FIG. 1 as 114 and 124. Also for example, sensor module 150F is oriented to detect one or more analytes in fluid from tissue in itssurrounding regions, identified in FIG. 1 as 120 and 124. Also by way ofexample, sensor module 150 G is oriented to detect one or more analytesin fluid from tissue in its surrounding regions, marked 120 and 122.

The term “analytes,” as used herein, includes biological analytesarising from biological tissue. Analytes can be indicative of neoplasiain breast tissue. Analytes can be detected by the sensor modulesdescribed herein. For example, analytes include proteins, polypeptides,peptides, nucleic acids, polysaccharides, lipids, saccharides,oligosaccharides, glycoproteins, glycolipids, and proteoglycans. In someembodiments, analytes can include lipid-protein combinations, anchoredproteins, lipoproteins, proteolipids and fatty acids. The specificanalyte or analytes detected by a particular implant system depend onthe sensor modules employed in that embodiment. In particular, analytesof interest include those that are indicative of abnormal cellulargrowth (e.g., neoplasms, malignancies, metastases, cancer) in orproximate to the breast although analytes can also indicate othercellular changes of medical interest in breast tissue. For example,analytes can include those indicative of the presence of breast cancer,the progression of breast cancer, or the initiation of breast cancer.For example, analytes can include those indicative of the presence ofmetastatic breast cancer and the translocation of breast cancer cells.For example, genetic amplification of the Her-2/neu oncogene isassociated with some metastatic breast cancers, and analytes associatedtherewith include regions of the extracellular domain of the Her-2/neuprotein (see Chourb et al., “Enhanced Immuno-detection of ShedExtracellular Domain of Her-2/neu,” Science Research 1(4): 325-329(2009), which is incorporated herein by reference). For example, somematrix metalloproteinases have been shown to be markers for breastcancers (see Roy et al., “Matrix Metalloproteinases as Novel Biomarkersand Potential Therapeutic Targets in Human Cancer,” Journal of ClinicalOncology, 27(31): 5287-5297 (2009), which is incorporated herein byreference). For example, analytes can include cancer markers such ascalreticulin, cellular retinoic acid-binding protein II, chlorideintracellular channel protein 1, EF-1-beta, galectin 1, peroxiredoxin-2,platelet-derived endothelial cell growth factor, protein disulfideisomerase and ubiquitin carboxyl-terminal hydrolase 5 (see Gromov etal., “Up-regulated Proteins in the Fluid Bathing the Tumour CellMicroenvironment as Potential Serological Markers for Early Detection ofCancer of the Breast,” Molecular Oncology 4: 65-89 (2010), which isincorporated herein by reference). For example, an analyte can includecancer antigen 15-3 (CA 15-3) (see Chourb et al., “Improved Detection ofthe MUC1 Cancer Antigen CA 15-3 by ALYGNSA Fluorimmunoassay,” ScienceResearch 3(8): 524-528 (2011), which is incorporated herein byreference). An analyte can include circulating microRNAs. For example,circulating microRNAs have been found that are indicative of breastcancer cells (see Vilaamil et al., “MicroRNA for circulating tumor cellsdetection in breast cancer: In silico and in vitro analysis,” 2009 ASCOAnnual Meeting Abstract No. e22027, J Clin Oncol 27, (2009) (suppl)which is incorporated herein by reference). An analyte can includesecreted exosomes. For example, secreted exosomes are indicative of sometumors (see Koga et al., “Purification, Characterization and BiologicalSignificance of Tumor-derived Exosomes” Anticancer Research 25:3703-3708 (2005), which is incorporated herein by reference). Forexample, an analyte can be Maspin (see Luppi et al., “SensitiveDetection of Circulating Breast Cancer Cells by Reverse-TranscriptasePolymerase Chain Reaction of Maspin Gene” Annals of Oncology, 7: 619-624(1996), which is incorporated herein by reference). For example,analytes can include mammaglobin and B305D-C (see Reinholz et al.,“Evaluation of a Panel of Tumor Markers for Molecular Detection ofCirculating Cancer Cells in Women with Suspected Breast Cancer,”Clinical Cancer Research 11: 3722-3732 (2005), which is incorporatedherein by reference). See: U.S. Pat. No. 5,668,267 to Watson andFleming, “Polynucleotides Encoding Mammaglobin, a Mammary-specificBreast Cancer Protein;” U.S. Pat. Nos. 5,855,889 and 5,968,754 to Watsonand Fleming “Mammaglobin, a Mammary-specific Breast Cancer Protein;”U.S. Pat. No. 5,922,836 to Watson and Fleming “Mammaglobin Antigens;”U.S. Pat. No. 6,004,756 to Watson and Fleming “Method for Detecting thePresence of Breast Cancer by Detecting an Increase in Mammaglobin mRNAExpression;” and U.S. Pat. Nos. 6,566,072 and 6,677,428 to Watson andFleming “Mammaglobin, a Secreted Mammary-specific Breast CancerProtein;” which are incorporated herein by reference.

The term “analytes,” as used herein, also includes analytes that areindicators, or markers, for tissue characteristics associated withtissue changes and neoplasia, such as: excessive cellular growth;inflammation; oxygen use; vascularization; and necrosis. For example, ithas been demonstrated that hypoxic regions of breast cancer massesexcrete the analyte lactate (see Semenza, “Tumor Metabolism: CancerCells Give and Take Lactate,” Journal of Clinical Investigation,118(12): 3835-3837 (2008), which is incorporated herein by reference).Other markers for hypoxia in solid tumors have been found (see Favaro etal., “Gene Expression and Hypoxia in Breast Cancer,” Genome Medicine,3(55) (2011), which is incorporated herein by reference). For example,multiple markers, including VPF/VEGF, flt-1, KDR, thrombospondin-1,collagen type I, fibronectin, versican and decorin, indicate thegeneration of vascular stroma in invasive breast carcinoma, breastcarcinoma in situ and metastatic breast carcinoma (see Brown et al.,“Vascular Stroma Formation in Carcinoma in Situ, Invasive Carcinoma, andMetastatic Carcinoma of the Breast,” Clinical Cancer Research 5:1041-1056, (1999) which is incorporated herein by reference). Forexample, analytes can include human epidermal growth factor receptor(hEGFR: see Li et al., “Inhibition of Cell Proliferation by an Anti-EGFRAptamer,” PLoS One, 6(6): e20299 (2011), which is incorporated herein byreference). For example, analytes can include markers of a reactivetumor stroma (see Radisky and Radisky, “Stromal Induction of BreastCancer: Inflammation and Invasion,” Rev Endocr Metab Disord. 8: 279-287(2007), which is incorporated herein by reference). In some embodiments,analytes include biochemical markers for inflammation, which canindicate a physiological reaction to the implant itself or a change inthe tissue independent of the implant.

Information from the plurality of sensor modules 150 A, B, C, D, E, Fand G integrated with the breast implant 140 described herein can assistin monitoring of breast tissue health and potential changes in breasttissue over time. By virtue of its capability of detecting analytes influid proximate to the breast implant 140, devices and systems describedherein can monitor a significant portion of the total breast tissue overtime from the interior of the breast for cellular changes, such as thedevelopment of neoplasia and cancer. The plurality of sensor modules 150A, B, C, D, E, F and G integrated with the breast implant 140 can detectanalytes present in interstitial fluid. The plurality of sensor modules150 A, B, C, D, E, F and G integrated with the breast implant 140 can beconfigured to detect analytes present in interstitial fluid proximal tothe breast implant 140. For example, information from the plurality ofsensor modules 150 A, B, C, D, E, F and G integrated with the breastimplant 140 described herein can assist in monitoring for breast cancer,hyperplasia, and related changes in breast tissue. For example,information from the plurality of sensor modules 150 A, B, C, D, E, Fand G integrated with the breast implant 140 described herein can assistin monitoring for cell changes within the tissue. Information from theplurality of sensor modules 150 A, B, C, D, E, F and G integrated with abreast implant 140 as described herein can be used by an individual andthe individual's medical team to inform decisions regarding furtherscreening, such as mammography, magnetic resonance imaging (MRI) exams,and needle biopsies. Some embodiments of the breast implants describedherein are configured to be compatible for further screening modalities.For example, some embodiments of the breast implants described hereinare configured to include minimal ferromagnetic material. For example,some embodiments of the breast implants described herein are configuredto be radiolucent. For example, some embodiments of the breast implantsdescribed herein include internal shielding. Information from theplurality of sensor modules 150 A, B, C, D, E, F and G integrated withthe breast implant 140 described herein can be used by an individual andthe individual's medical team to inform decisions regarding furtherscreening, such as mammography, magnetic resonance imaging (MRI) exams,and needle biopsies. Information from the plurality of sensor modules150 A, B, C, D, E, F and G integrated with the breast implant 140described herein can be used by an individual and her medical team todecide if further screening is warranted, or if such additionalscreening is not indicated at a particular time. In an embodiment, eachof the plurality of sensor modules (e.g., sensor modules 150 A, B, C, D,E, F and G as shown in FIG. 1) has its own unique identifier,information can be specified as arising from that specific module and,therefore, being relevant to the adjacent tissue. This informationinforms as to the appropriate region of the breast tissue that canwarrant further screening.

It is envisioned that the sensor modules utilized in the embodimentsdescribed herein can functionally persist in vivo for a period of years.Although a direct estimate of the duration of the functionality of aspecific sensor module depends on the specific embodiment, someembodiments envisioned herein are estimated to provide informationregarding analytes for a period of no less than 5 years after theimplantation surgery, while some are envisioned to provide informationregarding analytes in breast tissue for approximately 5 to approximately10 years after implantation and initiation of use. For example,embodiments including a number of sensor units that are uncovered oractivated over time can provide analyte detection over an extendedperiod of time. For example, some of the sensor units described hereinare estimated to provide functional analyte detection for a period ofyears. For example, some of the sensor units described herein may berecharged or refreshed. In some situations, a particular patient using abreast implant such as those described herein may choose to not have herbreast implant replaced when it ceases to function to monitor analytesfrom adjacent breast tissue. The implant structure itself will persistand continue to provide aesthetic benefits even without operationalsensor modules. The used or depleted sensor modules will be inert, andnot require removal. For example, a woman undergoing breastreconstruction after mastectomy may be most interested in analytedetection in the first five years after the initial cancer diagnosis, assuch detection may indicate a relapse or the persistence of cancer thatwas not adequately removed at the initial surgery. An implant such asdescribed herein may be desirable to monitor the five year post-cancerdiagnosis interval in a cancer patient after reconstruction. See TheAmerican Cancer Society., Breast Cancer Facts & Figures 2011-2012:Atlanta: American Cancer Society, Inc., which is incorporated herein byreference.

In some embodiments, breast implants can be configured to minimallyinterfere with further screening through other modalities. For example,a breast implant can be fabricated with no or minimal amounts offerromagnetic materials, so as to not potentially interfere with laterscreening techniques that employ magnetic resonance, such as MRIscreening. See, for example, US Patent Application Publication No.2011/077736 to Rofougaran, “Breast Implant System Including Bio-MedicalUnits,” which is incorporated herein by reference. For example, a breastimplant can be configured to form minimal shadowing in mammography, suchas being fabricated with materials that do not reflect or refractX-rays. For example, a breast implant can be configured forcompatibility with ultrasound screening, such as being fabricated withmaterials that do not reflect or refract ultrasound waves. In someembodiments, breast implants include shielding for one or more features.For example, a breast implant may include shielding of a power source.For example, a breast implant may include shielding of a wire connector.A breast implant 140 can include shielding to minimize disruption of thebreast implant by other screening modalities. See, for example, USPatent Application Publication No. 2007/0106332, “MRI CompatibleImplanted Electronic Medical Device,” to Denker et al., which isincorporated herein by reference.

Breast implants configured to detect different analytes will be ofinterest to different patients, for example women who have previouslyhad a breast cancer diagnosis (e.g. reconstructive surgery patients) incomparison with women who have not had a breast cancer diagnosis (e.g.augmentation surgery patients). A woman who has had a previous historyof breast cancer can choose a breast implant with sensor modulesconfigured to detect the type of cancer that she had previously, e.g. tomonitor for a reoccurrence. In contrast, a woman who has been neverdiagnosed with breast cancer can choose a breast implant with sensormodules that are configured to detect cellular changes indicative ofbreast cancer more generally, or other tissue changes that may havemedical consequences. For example, a woman who has been previouslydiagnosed with HER-2/Neu positive breast cancer may be concerned with arecurrence of the original cancer after mastectomy (i.e. regrowth of thetumor from a small number of tumor cells not removed at surgery) and,therefore, may choose a breast implant including sensor modulesconfigured to respond to Her-2/Neu. For example, a woman who haspreviously been diagnosed with estrogen receptor-positive breast cancer(ER+) may be concerned with recurrence of the original tumor afterlumpectomy and therefore, can choose a breast implant including sensormodules configured to respond to the presence of ER+ cells. For example,sensor modules in a breast implant can be configured to respond to thepresence of abnormally high levels of estrogen receptor, such as foundin some cancer tissues. For example, a woman without a history of breastcancer diagnosis can choose a breast implant for use in augmentationsurgery that is configured to detect indicators of breast cancergenerally, such as mammoglobin, maspin, or matrix metaloproteinases. Forexample, a woman without a history of breast cancer diagnosis can choosea breast implant for use in augmentation surgery that is configured todetect indicators of tissue inflammation in the breast. For example, awoman without a history of breast cancer diagnosis can choose a breastimplant for use in augmentation surgery that is configured to detectindicators of neoplastic growth, such as vascularization, hypoxia,increased cellular division, and necrosis. See also: American CancerSociety., Breast Cancer Facts & Figures 2011-2012: Atlanta: AmericanCancer Society, Inc., which is incorporated herein by reference.

The analytes detected by the sensor modules are present in the fluid inthe tissue adjacent to the breast implant, which can includeinterstitial or extracellular fluid, lymph, and blood. Multiple studieshave indicated that cells, including cancer cells, release cellularcomponents into the interstitial or extracellular fluid in tissue, andthat such cellular components are indicative of the originating celltype. Proteins secreted from tumor cells, or a portion of the“secretome,” can serve as markers for the presence of tumor cells. See,for example: Kulasingham and Diamandis, “Tissue Culture-based BreastCancer Biomarker Discovery Platform,” International Journal of Cancer123: 2007-2012 (2008); and Wiig et al., “Interstitial Fluid: theOverlooked Component of the Tumor Microenvironment?” Fibrogenesis &Tissue Repair 3:12 (2010), which are each incorporated herein byreference. Surface proteins shed from cells can also serve as markersfor the presence of tumor cells. In some embodiments, whole or partialcancer cells, such as metastatic cells, can be detectable via theirspecific surface proteins.

Referring again to FIG. 1, the breast implant 140 includes a shell 145,which is substantially filled with a viscous material configured toimpart shape and texture to the breast 100. Some embodiments include lowprofile implants. The viscous material is compatible with biologicalimplants. For example, the shell 145 can be substantially filled with asaline solution. For example, the shell 145 can be a silicone-basedbarrier layer substantially filled with silicone gel. For example, thebreast implant 140 can include a shell 145 fabricated from a single gelbarrier layer configured to surround an elastomeric gel, as described inU.S. Pat. No. 8,043,373 “All-Barrier Elastomeric Gel-Filled BreastProsthesis,” to Schuessler and Powell, which is incorporated herein byreference. For example, the breast implant 140 can include a shell 145configured to include a variable cohesive gel, such as described in U.S.Pat. No. 8,070,808 “Variable Cohesive Gel Form-Stable Breast Implant” toMaxwell et al., which is incorporated herein by reference. For example,the breast implant 140 can include a shell 145 that includes internalpartitions configured to be surrounded by a fluid gel, such as describedin U.S. Pat. No. 3,559,214 “Compound Prosthesis” to Pangman, which isincorporated herein by reference. The breast implant 140 can includeother internal features, such as reservoirs, ports, expandable regions,sealing regions and stabilizing features. See, for example US PatentApplication No. 2011/0208302 “Reconstructive Breast Prosthesis” toGlicksman, which is incorporated herein by reference. The breast implant140 can include a minimally invasive profile during implantationsurgery, such as described in International PCT Publication No. WO2008/014283 to Burnett, “Method and Apparatus for Minimally InvasiveImplants” which is incorporated herein by reference.

The shell 145 of the breast implant 140 can include a single layer, suchas of elastomeric polymer or firm silicone. The shell 145 of the breastimplant 140 can be fabricated from a bio-compatible material. The shell145 is configured to maintain the structural integrity of the implantwithout rupture or leakage of the viscous material inside the shell 145.In some embodiments, a breast implant 140 includes a shell 145 thatincludes at least two barrier layers. For example, a breast implant 140can include a shell 145 made up of two or more layers of silicone. Forexample, a breast implant 140 can include a shell 145 fabricated fromtwo or more sheets of elastomeric polymer. A shell 145 of a breastimplant 140 can include a plurality of barrier layers, or layers ofmaterial configured to maintain the structural integrity of the implantwithout rupture or leakage. The breast implant 140 can include a shellwith electrically insulating properties surrounding a low-conductancefiller material, such as described in International PCT Publication No.WO 2008/014283 to Burnett, “Method and Apparatus for Minimally InvasiveImplants” which is incorporated herein by reference.

The breast implant 140 includes at least one fluid-permeable cover 155completely enveloping the shell 145. For example, as illustrated in FIG.1, a cover 155 surrounds the shell 145 with a gap 160 between the cover155 and the shell 145. In some embodiments, a cover 155 is configured tocompletely envelop the shell 145 with a uniform gap 160 between thecover 155 and the shell 145. In some embodiments, a cover 155 has aninternal diameter that is larger than the largest exterior diameter ofthe shell 145. As shown in FIG. 1, in some embodiments a cover 155 isapproximately the same shape as the shell 145 to maintain a uniform gap160 between the shell 145 and the cover 155. A plurality of projections165 form a series of compartments in the gap 160 between the shell 145and the cover 155. Each projection extends from an outer surface of theshell 145 to an inner surface of the cover 155. During use, interstitialfluid from the tissue adjacent to the breast implant 140 (e.g. asidentified as 112, 110, 114, 124, 120 and 122 in FIG. 1) will move intothe gap 160 adjacent to the sensor modules 150 A, B, C, D, E, F and Goriented around the exterior of the breast implant 140 (illustrated withthe dotted arrows in FIG. 1). The cover 155 can be configured to filterexcess cellular material from the breast implant 140, including thesensor modules 150, and therefore prevent clogging or fouling of thesensor modules 150. The cover 155 can be configured to preventlymphocytes and other immune response cells from interacting with thesurface of the shell 145 and the sensor modules 150, thereby minimizingimmune response to the breast implant 140 over time. The cover 155 canbe configured to encourage normal cellular growth in the tissue adjacentto the breast implant 140, thereby increasing fluid flow through theregion and minimizing the formation of scar tissue. The breast implant140 can include a cover 155 fabricated from an analyte-permeablematerial. For example, the cover 155 may include pores or openings ofsufficient size and shape to allow analytes detectable by the sensormodules 150 to flow through the cover 155. In a particular embodiment,the cover 155 can be permeable to one or more type of analytescorresponding to types of analytes detected by the sensor modules 150and largely impermeable to other analytes. For example, the cover 155can include pores or holes of a size and shape to exclude materialpresent in interstitial fluid that is larger than the analyte(s)detected by the sensor modules 150 attached to the shell 145. Forexample, the cover 155 can include pores or holes of a size and shape toexclude whole lymphocyte or epithelial cells, while permitting themovement of proteins, nucleic acids, polysaccharides, and other cellularcomponents through the cover 155. The breast implant 140 can include acover 155 fabricated from an analyte-permeable material that promotesthe movement of a specific analyte or type of analytes through the cover155. For example, the cover 155 can include a surface charge thatattracts types of analytes corresponding to analytes detected by thesensor modules 150 in a particular embodiment, and repelling other typesof analytes. The breast implant 140 can include a cover 155 fabricatedfrom a variety of materials, depending on the embodiment. For example,the breast implant 140 can include a cover 155 fabricated from a plasticmaterial, or from a fabric material. For example, the cover 155 caninclude polytetrafluoroethylene (PTFE) (e.g. Teflon™ or Gore-tex™materials). For example, the breast implant 140 can include a cover 155fabricated from a bio-compatible material. The breast implant 140 caninclude a cover 155 fabricated from a mesh structure. The breast implant140 can include a cover 155 fabricated from a porous structure. Forexample, a cover 155 with a porous structure can include pores that areconfigured to form a biocompatible layer between the cover 155 and theadjacent tissue. See, for example, US Patent Application No.2011/0282444 to Liu et al., “Porous Materials, Methods of Making andUses” which is incorporated herein by reference. The breast implant 140can include a cover 155 with a fluid control film component oriented topermit directional flow of interstitial fluid into and out of the gap160. See, for example, U.S. Pat. No. 6,420,622 to Johnston et al.,“Medical Article Having Fluid Control Film,” which is incorporatedherein by reference. The breast implant 140 can include a cover 155 withproperties that inhibit tumor cell growth. See, for example, Zhang andWebster, “Poly-lactic-glycolic-acid surface nanotopographies selectivelydecrease breast adenocarcinoma cell functions,” Nanotechnology 23:155101 (2012), which is incorporated herein by reference. The breastimplant 140 can include a cover 155 with a three dimensionalconformation or architectural structure at the host interface thatpromotes close vascularization from the tissue immediately surroundingthe implant 140 (e.g. as identified as 112, 110, 114, 124, 120 and 122in FIG. 1), thereby increasing the adjacent fluid available forsampling. See, for example, U.S. Pat. No. 5,800,529 to Brauker et al.,“Close Vascularization Implant Material,” which is incorporated hereinby reference. A cover 155 can include a biointerface membrane configuredto improve the biointerface between implantable devices and the adjacenttissue. See, for example, U.S. Pat. No. 7,364,592 to Carr-Brendel etal., “Biointerface Membrane with Macro- and Micro-Architecture,” whichis incorporated herein by reference. A cover 155 can include anadditional coating. See U.S. Pat. Nos. 6,119,028 and 6,477,395,“Implantable Enzyme-Based Monitoring Systems Having Improved LongevityDue to Improved Exterior Surfaces,” to Schulman et al., which are eachincorporated herein by reference. A cover 155 can be fabricated frommaterials expected to provide a natural feel to the breast implant 140,for example silicone or soft polymer. A cover can be configured toprovide texture or cushioning to a breast implant 140 to improve theaesthetics of the breast implant 140.

A plurality of projections 165 extend from an external surface of theshell 145, the projections 165 forming a plurality of compartmentsadjacent to the external surface of the shell 145. The projections 165can be configured as partitions. The plurality of projections 165 can beconfigured as a plurality of membranes attached to the external surfaceof the shell 145. For example, the plurality of projections 165 can beconfigured as a plurality of membranes attached to the external surfaceof the shell 145 with a fluid-resistant seal at the junction between theexternal surface of the shell 145 with the plurality of projections 165.The projections 165 can include a first end surface sealed to theexternal surface of the shell, and a second end surface sealed to asurface of the cover. The projections 165 form a series of compartmentsadjacent to the surface of the shell 145, for example around the sensormodules 150 on the surface of the shell 145. Some embodiments includeone sensor module 150 in each compartment. Some embodiments include aplurality of sensor modules 150 in each compartment. The compartmentscan include a region of the cover forming a side of each of thecompartments, the region including at least one set of influxmicrochannels configured to direct fluid into the compartment, andincluding at least one set of efflux microchannels configured to directfluid out of the compartment. The compartments can be substantiallysealed from each other. For example, each of the compartments can beimpenetrable to direct transfer of fluid from compartment tocompartment. The compartments can be oriented with an approximate axisfrom the top of the breast implant to the bottom, with direction asexpected during in vivo use. For example, the compartments can beoriented with an approximate axis from the top of the breast implant tothe bottom, so that gravity can be expected to assist in fluid flow fromthe top to the bottom through each compartment during in-vivo use. Thecompartments can be substantially sealed from each other. For example,the compartments can be positioned and configured to minimize fluid flowdirectly between the compartments.

FIG. 1 also illustrates that the breast implant 140 includes a pluralityof sensor modules 150 A, B, C, D, E, F and G oriented around theexterior of the breast implant 140. It will be appreciated that eventhough FIG. 1 depicts seven sensor modules, any number of sensor modulescan be used. The sensor modules 150 A, B, C, D, E, F and G are orientedto detect one or more analytes in a fluid arising from a positionbetween the shell 145 and the cover 155, such as in interstitial fluidfrom the surrounding tissue. The sensor modules 150 A, B, C, D, E, F andG are positioned at a distance from each other around the exteriorsurface of the shell 145. The sensor modules 150 A, B, C, D, E, F and Gcan be positioned in a substantially regular orientation around thecircumference of the shell 145. As discussed further below, some of thesensor modules 150 A, B, C, D, E, F and G can be clustered around thesurface of the shell 145 to more fully monitor a region or area ofadjacent breast tissue. In some embodiments, the sensor modules can bepositioned in an irregular orientation, for example to morecomprehensively monitor a specific adjacent region of tissue, such as aprevious cancer site or another region of interest. The sensor modules150 A, B, C, D, E, F and G can be oriented to function as an array, aweb or as part of a nodal network. The sensor modules 150 A, B, C, D, E,F and G are oriented and positioned to monitor analytes in fluid fromthe breast tissue surrounding the breast implant 140. The sensor modules150 A, B, C, D, E, F and G can be configured to detect one or morebiological analytes arising from biological tissue, such as the breasttissue adjacent to a specific sensor module. The sensor modules 150 A,B, C, D, E, F and G can be oriented and positioned to monitor analytesin fluid from a comprehensive sampling of the breast tissue surroundingthe breast implant 140. The region of breast tissue monitored and thesensitivity of the monitoring depends on factors including the type ofsensor modules, the position of the sensor modules, the orientation ofthe sensor modules, and the density of the sensor modules. The sensormodules 150 A, B, C, D, E, F and G shown in FIG. 1 are positioned andoriented to detect analytes in interstitial fluid substantially aroundthe entire periphery of the breast implant 140.

Devices and systems described herein can monitor a significantpercentage of the tissue within the total interior of a breast over timefor cellular changes, such as the development of cancer, by detectinganalytes in interstitial fluid around the entire periphery of the breastimplant 140. In some embodiments, the sensor modules are positioned toenhance monitoring of tissue in one or more regions of particularinterest. Although the size and positioning of particular breastimplants will vary depending on the specific individual patient andbreast tissue morphology, a breast implant 140 includes a shell 145 anda cover 155 with an external surface that is positioned within andadjacent to breast tissue.

Different breast implants will be fashioned in different sizes andshapes, and sensor modules can be of any range of sizes. The positioningand total number of sensor modules attached to a breast implant willvary depending on the embodiment. As breast implant sizes depend on thespecific embodiment, the corresponding space available for the placementof sensor modules depends on the specific implant. The breast implant140 illustrated in FIG. 1 is depicted as an elongated teardrop shapewith a flattened back region, but in some embodiments a breast implant140 will be configured as an ellipse, an ovoid, a disk or other shape.Therefore, depending on the shape and size of the breast implant 140utilized in a given embodiment, the potential positions and numbers ofsensor modules 150 will vary. However, for a breast implant 140 of anygiven shape and size, the number and position of sensor modules 150around the circumference of the shell 145 will be selected to providesampling of fluid adjacent to the periphery of the cover 155.

In some embodiments, sensors may be clustered or oriented to provideadditional monitor capability in regions of breast tissue of particularinterest. For example, a region of a breast implant 140 adjacent to theoriginal tumor locus can have additional sensor modules 150 for use inreconstructive surgery. For example, a region of the breast implant 140that may be adjacent to a breast tissue region difficult to visualizethrough mammography, such as a region of the implant 140 positionedadjacent to the chest wall (e.g. regions 122, 120 and 124 in FIG. 1) canhave additional sensor modules 150 to provide additional monitoringcapability in that tissue region.

In some embodiments, such as illustrated in FIGS. 1 and 2, sensormodules 150 of a single type are attached to and approximately equallydistributed around the external surface of the shell 145 of the breastimplant 140. However, in some embodiments, regions of unequal densityand/or sensor module types may be fabricated and implemented. In someembodiments, sensor modules 150 are positioned on a breast implant 140in a region of interest for monitoring. For example, in an embodimentwherein the region adjacent to the chest wall is of particular interestin monitoring for cellular changes, the region of the shell 145 of thebreast implant 140 configured to be positioned adjacent to the chestwall may have a higher density of sensor modules 150 attached than otherregions of the breast implant 140.

In some embodiments, sensor modules 150 of particular types may beattached to particular regions of the shell 145 of the breast implant140. For example, sensor modules 150 configured to detect changes inductal breast tissue may be attached to the region of the shell 145 ofthe implant 140 adjacent to most of the ductal tissue (e.g. afront-facing portion of the implant 140) in a particular individual. Forexample, sensor modules 150 configured to detect changes in breasttissue in the regions of the chest wall may be attached to the region ofthe shell 145 of the implant 140 adjacent to the chest wall (e.g. arear-facing portion of the implant 140) in a particular individual. Insome embodiments, some regions of the shell 145 of the breast implant140 are left with few or none sensor modules 150 and other regionsinclude a dense coverage of sensor modules 150.

In some embodiments and as illustrated in FIG. 1, each of the sensormodules 150 includes a unique identifier for that sensor module 150. Forexample, FIG. 1 includes sensor modules 150 A, B, C, D, E, F and G,wherein each of the letter designations represents a unique identifierfor that sensor module 150. A unique identifier for a sensor module 150is a specific identifier that denotes that sensor module 150 (e.g. 150A) and no other sensor module 150 (e.g. 150 B, C, D, E, F and G). As anadditional example, FIGS. 3, 4, 5 and 6 include sensor modules 150 A, B,C, and D, wherein each of the letter designations represents a uniqueidentifier for that sensor module 150. In some embodiments, a uniqueidentifier associated with a sensor module includes an alphanumericcode. An alphanumeric code is made up of some combination of letters andnumbers, such as 123, ABC, 12B34, AB34CD, or similar codes. In someembodiments, a unique identifier for a sensor module includes apositional identifier. A positional identifier includes informationrelative to the specific size and shape of a particular breast implant140. For example, a positional identifier for a sensor module mayinclude positional information such as “upper right front corner” or“lower center of rear face” or similar information. For example, apositional identifier for a sensor module may include positionalinformation such as “grid location 1A” or “intersection of gridlines Xand Y.” In some embodiments, a unique identifier for a sensor moduleincludes an electronic code, such as a radio frequency identification(RFID) identifier code. In some embodiments, a unique identifier for asensor module includes a digital code. In some embodiments, a uniqueidentifier for a sensor module includes an analog code. In someembodiments, a unique identifier for a sensor module includes a machinecode. In some embodiments, sensor modules of a particular type can havea common identifier; wherein such identifier is different from those ofsensor modules of a different type.

FIG. 2 illustrates further aspects of a breast implant 140 with aplurality of attached sensor modules 150. Illustrated in FIG. 2 is anexternal, ex-vivo view of a breast implant 140. FIG. 2 illustrates anembodiment wherein the plurality of sensor modules 150 attached to theshell 145 of the breast implant 140 are substantially equally positionedover the surface of the shell. A cover 155 completely surrounds andenvelops the shell 145. A gap 160 is located between the cover 155 andthe shell 145. A series of projections 165 are arranged in a grid-likearray over the surface of the shell 145. In the view shown in FIG. 2,the projections are configured as flat sheets surrounding thecircumference of the shell 145 and positioned at approximate rightangles to the shell 145. FIG. 2 illustrates the projections 165 aspartitions between the plurality of compartments 200. In the view shownin FIG. 2, the projections form a plurality of compartments 200, each ofthe compartments 200 including a sensor module 150. The plurality ofsensor modules 150 attached to the shell 145 of the breast implant 140shown in FIG. 2 are attached in an approximately even distribution onthe shell 145 surface. The plurality of sensor modules 150 attached tothe shell 145 of the breast implant 140 shown in FIG. 2 are attached ina grid-like array. The flat view illustrated in FIG. 2 is a depiction ofa plurality of sensor modules 150 attached to the shell 145 of thebreast implant 140 and does not fully represent the 3-dimensional natureof the distribution of the sensor modules 150 and the compartments 200on a shell 145 that is substantially curved or includes an arcstructure.

A breast implant 140 can include a grid over the surface of the shell145 of the breast implant 140. A grid can be visible, invisible to astandard observer, or virtual. Position-indicating lines can serve todescribe regions of the surface of the shell 145 of a breast implant140. For example, intersecting lines can indicate the location on thesurface of the shell 145 corresponding to the location of a particularsensor module. The location of the particular sensor module can beidentified as the “intersection of line X and line Y.” Similarly,regions of a shell 145 surface including more than one sensor module 150can be identified by the positional lines surrounding that region of theshell 145 surface. Some embodiments can include grid lines in anirregular or uneven pattern, for example to correspond to the surfaceshape of a breast implant 140 of an irregular or uneven shape. Someembodiments can include other positional marks, such as edgeidentifiers, quadrant positional marks, or similar identifiers ofposition on the surface of the shell 145. Some embodiments can includepositional marks that are not visible, such as virtual marks based onphysical features of the breast implant 140, such as “a location 3 cmfrom the upper right quadrant” or similar positional information. Someembodiments can include fiducial markers.

Further aspects of a breast implant 140 are illustrated in FIG. 3. FIG.3 shows a cross-sectional view of a breast implant 140 ex-vivo. FIG. 3illustrates a breast implant 140 with an outer shell 145 and an interior300 configured to be substantially filled with a viscous material. Acover 155 completely surrounds and envelops the shell 145 with a gap 160between the shell 145 surface and the cover 155 surface. A plurality ofprojections 165 extend from an external surface of the shell 145, theprojections 165 forming a plurality of compartments 200 A, B, C, Dadjacent to the external surface of the shell 145. In the view shown inFIG. 3, sensor modules 150 A, 150 B, 150 C and 150 D are distributedapproximately equally around the external surface of the shell 145. FIG.3 illustrates an embodiment wherein the breast implant 140 has been cutapproximately in half along a plane corresponding to the widest part ofthe breast implant 140. In general, the implant 140 is of a size andshape desirable in a particular embodiment and the sensor modules 150 A,B, C and D are correspondingly positioned relative to each other. Forexample, a breast implant 140 that is approximately 12.5 cm across (e.g.in a straight line between sensor modules 150 D and 150 B) andapproximately 12 cm long (e.g. in a straight line between sensor modules150 A and 150 C), the total perimeter of the breast implant 140 would beapproximately 76 cm and the distance between the center of each sensormodule 150 (e.g. 150 A) and its adjacent sensor modules 150 (e.g. 150 Dand 150 B) would be approximately 19 cm along the surface of the shell145. For example, embodiments can include breast implants including aplurality of sensor modules attached to the shell, and wherein thecenters of the sensor modules attached to the shell are separated bydistances of approximately 5 cm to approximately 8 cm. For example,embodiments can include breast implants including a plurality of sensormodules attached to the shell, and wherein the centers of the sensormodules attached to the shell are separated by distances ofapproximately 3 cm to approximately 6 cm. For example, embodiments caninclude breast implants including a plurality of sensor modules attachedto the shell, and wherein the centers of the sensor modules attached tothe shell are separated by distances of approximately 1 cm toapproximately 4 cm. For example, embodiments can include breast implantsincluding a plurality of sensor modules attached to the shell, andwherein the centers of the sensor modules attached to the shell areseparated by distances of less than approximately 1 cm. Some embodimentsthat include sensor modules fabricated on a microsensor scale or ananosensor scale, with corresponding small distances between the sensormodules.

FIG. 3 illustrates that each of the sensor modules 150 A, B, C, D arepositioned and oriented on the shell 145 of the breast implant 140 sothat each sensor module 150 A, B, C, D can monitor analytes in fluidfrom a specific region of breast tissue. Each of the sensor modules 150A, B, C, D is positioned on the surface of the shell 145 at a distancefrom each other. Each of the sensor modules 150 A, B, C, D is orientedon the surface of the shell 145 to detect one or more analytes in afluid within one of the plurality of compartments 200 A, B, C, D. Asshown in FIG. 3, sensor module 150 A is positioned to monitor analytesin fluid in compartment 200 A, the fluid arising from tissue in theadjacent region identified as 310. FIG. 3 also illustrates that sensormodule 150 B is oriented to monitor analytes in fluid in compartment 200B, the fluid originating from tissue in the adjacent region identifiedas 395. FIG. 3 shows sensor module 150 C oriented to monitor analytes influid in compartment 200 C, the fluid originating from the adjacenttissue region indicated as 350. FIG. 3 also illustrates sensor module150 D positioned to monitor analytes in fluid in compartment 200 D, thefluid arising from tissue in the adjacent region 370.

Since each of the sensor modules 150 A, B, C, D can also include its ownunique identifier, any information regarding detected analytes in fluidwhile the breast implant 140 is in use is also informative for thecorresponding adjacent region of tissue. For example, during in-vivo usean analyte in a fluid detected by sensor module 150 A can be expected tohave arisen from adjacent tissue region 310. As an additional example,during in-vivo use a positive signal for an analyte arising from sensormodule 150 B and including the specific identifier of sensor module 150B can be assumed to come from an analyte flowing to the sensor module150 B in fluid from tissue region 395. Also for example, if sensormodule 150 C detects an analyte, that analyte can be expected to havearisen in the region of adjacent tissue identified as 350. As a furtherexample, if information from sensor module 150 D indicates that ananalyte has been detected, the analyte can be expected to have come fromfluid in region 370. Identification of the region of tissue that ananalyte is expected to have arisen from provides an individual and theindividual's health care team information as to where a possible changein breast tissue has occurred, and therefore a region to focus furtherscreening efforts. For example, a region of breast tissue with apositive indicator may be further screened through palpation or biopsyof the region. For example, a region of breast tissue with a positiveindicator may be further screened through focused imaging such asultrasound, MRI or mammography.

As illustrated in FIG. 3, the sensor modules 150 A, B, C, D can bepositioned so that there is some overlap in the adjacent tissue that thesensor modules 150 A, B, C, D are reasonably expected to monitor fluidfrom during the expected use of the breast implant 140. Positioning thesensor modules 150 A, B, C, D in close enough proximity for overlappingregions of tissue to monitor fluid arising from them can reduce thechance that an analyte in tissue fluid adjacent to the breast implant140 will fail to be detected by at least one of the sensor modules 150A, B, C, D. Positioning the sensor modules 150 A, B, C, D withoverlapping regions of sensitivity can also assist in locating theregion of adjacent breast tissue that is a candidate for furtherscreening. For example, if a system provides information that bothsensor modules 150 A and 150 B have detected an analyte in fluid, thefluid can be expected to have been in the overlapping monitoring tissueregion for both sensor modules A and B (illustrated in FIG. 3 as region320). For example, if sensor modules 150 B and 150 C both detect ananalyte in fluid from adjacent tissue, further screening can be focusedon the tissue region that includes the sensitivity region of both sensormodule 150 B and 150 C (e.g. region 390 in FIG. 3). As a furtherexample, if both sensor modules 150 C and 150 D provide information thatthey have detected an analyte at a similar time, the analyte can havearisen in fluid from tissue region 360, and that region of breast tissuecan be the focus of further screening. Also by way of example, ifinformation arising from sensor modules 150 D and 150 A indicates thatan analyte is present in the adjacent tissue of both sensor modules, anadjacent region such as indicated at 380 in FIG. 3 can be the subject offurther screening.

Sensor modules can be attached to the surface of the shell using avariety of techniques. For example, in embodiments wherein the sensormodules are attached to an external surface of the 150 A, B, C, D, suchas illustrated in FIG. 3, the sensor modules can be affixed to thesurface using an adhesive. In some embodiments, one or more aspects ofsensor modules are directly printed onto the surface of the shell.

FIG. 4 illustrates further aspects of a breast implant 140. The breastimplant 140 depicted in FIG. 4 is shown in cross-section, a similar viewas FIG. 3. However, the breast implant illustrated in FIG. 4 is adifferent embodiment than that illustrated in FIG. 3. FIG. 4 shows abreast implant 140 including a shell 145 configured to be substantiallyfilled with a viscous material 300. A cover 155 completely surrounds andenvelops the shell 145 with a gap 160 between the shell 145 surface andthe cover 155 surface. A plurality of projections 165 extend from anexternal surface of the shell 145, the projections 165 forming aplurality of compartments 200 A, B, C, D adjacent to the externalsurface of the shell 145. The breast implant 140 illustrated in FIG. 4includes a plurality of sensor modules 150 A, B, C and D positioned atapproximately equal distances from each other around the surface of theshell 145. Each compartment 200 A, B, C, D includes a sensor module 150A, B, C, D. Each of the sensor modules 150 A, B, C, D is oriented todetect one or more analytes in a fluid within one of the plurality ofcompartments 200 A, B, C, D. Each of the sensor modules 150 A, B, C andD includes a unique identifier (not shown in FIG. 4). Each of the sensormodules 150 A, B, C and D is configured to utilize energy transmittedfrom an external source. Each of the sensor modules 150 A, B, C and Dcan be configured to utilize energy transmitted from an ex-vivo source.As shown in FIG. 4, a breast implant 140 can include a plurality ofenergy transfer units 450 A, B, C, D. Each of energy transfer units 450A, B, C, D are attached to the exterior of the shell 145. Each of theenergy transfer units 450 A, B, C, D includes an antenna 420 A, B, C, Dand each of the energy transfer units includes an energy harvesting unit440 A, B, C, D. As shown in FIG. 4, one energy transfer unit, 450 A, isoperably attached to sensor module 150 A with a wire connection 430 A.Also as shown in FIG. 4, one energy transfer unit, 450 B, is operablyattached to sensor module 150 B with a wire connection 430 B. FIG. 4illustrates one energy transfer unit, 450 C, operably attached to sensormodule 150 C with a wire connection 430 C. FIG. 4 also depicts oneenergy transfer unit, 450 D, connected to sensor module 150 D with awire connection 430 D. The wire connections 430 A, B, C, D arepositioned adjacent to the exterior surface of the shell 145. Althoughnot illustrated in FIG. 4, in some embodiments the energy transfer unit450 can include memory. For example, an energy transfer unit 450 caninclude a passive data logger, as described in Yeager et al.,“Wirelessly-Charged UHF Tags for Sensor Data Collection,” 2008 IEEEInternational Conference on RFID, Apr. 16-17, 2008, pages 320-327, whichis incorporated herein by reference. Although not illustrated in FIG. 4,in some embodiments the energy transfer unit 450 can include aprocessor. For example, the energy transfer unit 450 can include apassive RFID unit and an associated processor.

The specific type of energy transfer unit 450 A, B, C, D included in aspecific embodiment depends on the type of energy utilized in theembodiment. Correspondingly, an antenna 420 and energy harvesting unit440 are configured to utilize an energy source relevant to a specificembodiment. Representative examples of energy sources includeelectromagnetic waves in the radio frequency range(s) and the infraredrange of the spectrum, as well as ultrasound energy.

An energy transfer unit 450 A, B, C, D can include a radio frequencyidentification (RFID) antenna 420 and associated power harvesting unit440. See, for example, Bradford et al., “Wireless Power and DataTransmission for a Pressure Sensing Medical Implant,” BMT October 2010.Radio frequency energy can be in the UHF band, or approximately 902-928MHz in the United States. See the “Worldwide RFID UHF Map” byIntelleflex Corporation (©2009), which is incorporated herein byreference. Radio frequency energy can be in a frequency range less thanapproximately 135 KHz, or consistent with the ISO 11784, ISO 11785,ISO/IEC 18000-2 and ISO 14223-1 standards. Radio frequency energy can bein a frequency range of approximately 13.56 MHz, or consistent with theISO/IEC 18000-3, EPC class-1, ISO 15693 and ISO 14443 (A/B) standards.See Chawla and Ha, “An Overview of Passive RFID,” IEEE Applications andPractice, 11-17 (September 2007), which is incorporated herein byreference. The antenna 420 can be an antenna configured to operate inthe radio frequency (e.g. RFID) spectrum. In some embodiments an antenna420 can include a self-compensating antenna. See, for example, U.S. Pat.No. 7,055,754 to Forster, titled “Self-Compensating Antennas forSubstrates Having Differing Dielectric Constant Values,” which isincorporated herein by reference.

In some embodiments, the energy transfer unit 450 A, 450 B is aninductive power harvesting unit. For example, an energy transfer unitcan include an inductive power harvesting unit such as described in USPatent Application No. 2010/0070003, “Systems configured to power atleast one device disposed in a living subject, and related apparatusesand methods,” to Hyde et al., which is incorporated herein by reference.For example, an energy transfer unit can include an inductive powerharvesting unit such as described in US Patent Application No.2010-0295372, “Methods, devices and systems for transmission between animplanted device and an external device,” to Hyde et al., which isincorporated herein by reference. For example, an energy transfer unitcan include an inductive power harvesting unit such as described in USPatent Application No. 2010-0070002, “Systems configured to locate aphotonic device disposed in a living subject, and related apparatusesand methods,” to Hyde et al., which is incorporated herein by reference.For example, an energy transfer unit can include an inductive powerharvesting unit such as described in US Patent Application No.2010-0065097, “Systems configured to deliver energy out of a livingsubject, and related apparatuses and methods,” to Hyde et al., which isincorporated herein by reference. For example, an energy transfer unitcan include an inductive power harvesting unit such as the inductivecoupling units described in Laskovsi and Yuce, “Class-E Oscillators asWireless Power Transmitters for Biomedical Implants” 3rd InternationalSymposium on Applied Sciences in Biomedical and CommunicationTechnologies, ISABEL 2010, (2010) and Laskovski et al., “Wireless PowerTechnology for Biomedical Implants,” Biomedical Engineering, In-Tech,Vukovar, Croatia, 119-132 (2009), which are each incorporated herein byreference.

An antenna 420 can include dielectric material configured toelectrically interact with one or more antennas. See, for example, U.S.Pat. No. 7,055,754 to Forster, titled “Self-Compensating Antennas forSubstrates Having Differing Dielectric Constant Values,” which isincorporated herein by reference. In some embodiments, the energytransfer unit 450 A, B, C, D is a photovoltaic collector. See, forexample, US Patent Application No. 2011/0044694, “Systems and Methodsfor Optically Powering Transducers and Related Transducers,” to Schereret al., which is incorporated herein by reference. See also Ayazian andHassibi, “Delivering Optical Power to Subcutaneous Implanted Devices,”33^(rd) Annual International Conference of the IEEE EMBS, Boston Mass.August 30- Sep. 3, 2011, pages 2874-2877, which is incorporated hereinby reference.

In some embodiments, the energy transfer unit 450 A, 450 B is amicroelectricalmechanical device configured to harvest ambient energyfrom in vivo sources. See, for example, Lueke and Moussa, “MEMS-BasedPower Generation Techniques for Implantable Biosensing Applications,”Sensors 11: 1433-1460 (2011), which is incorporated herein by reference.

In the embodiment illustrated in FIG. 4, the entire energy transfer unit450, including the antenna 420 and the energy harvesting unit 440, ispositioned on the shell 145. In the illustration of FIG. 4, the entireenergy transfer unit 450 is positioned within the sphere of the cover155. A cover 155 for an embodiment such as illustrated in FIG. 4 shouldbe chosen to allow the antenna 420 to receive the signals required forthe embodiment to function, with minimal disruption and effectivepropagation of the relevant signals through the cover. In someembodiments, an antenna 420 can be positioned in whole or relevant partoutside of the outer surface of the cover 155 to allow for propagationof signals to and from the antenna 420 without disruption by the cover155. In some embodiments, the energy harvesting unit 440 in whole or inpart can be positioned to maximize propagation of signals to and fromrelevant regions of the energy harvesting unit 440. In some embodiments,the energy harvesting unit 440 in whole or in part can be embeddedwithin the cover 155. In some embodiments, the energy harvesting unit440 can be positioned in whole or in part within an aperture in thecover 155. The energy harvesting unit 440 can be attached to a surfaceof the cover 155.

FIG. 4 also illustrates a breast implant 140 wherein the shell 145comprises a plurality of barrier layers. The different layers canprovide, for example, additional protection against leakage of theinterior viscous material 300 out of the breast implant 140 over asingle barrier layer. The different layers can provide, for example,additional structure, such as for support for the sensor modules 150 A,B, C, D and the energy transfer units 450 A, B, C, D. The differentlayers can provide, for example, structure to stabilize the projections165. The shell 145 illustrated in FIG. 4 includes two barrier layers400, 410. The barrier layers 400 410 are substantially similar sizes andshapes, with the inner barrier layer 400 within and slightly smallerthan the outer barrier layer 410. In FIG. 4, the barrier layers 400, 410are in a nesting configuration relative to each other with a minimalvolume of space between the layers 400, 410. In some embodiments, aplurality of barrier layers can be of different sizes, with a largervolume of space between the layers. The plurality of layers may be ofdifferent shapes with relative sizes to allow the layers to nest withineach other. Structural features of the breast implant 140 may bepositioned between barrier layers of the shell 145, and may be attachedto one or more of the barrier layers. For example, all or part of one ormore energy transfer unit 450 A, B, C, D may be positioned within thebarrier layers 400, 410 of the shell 145 (e.g. between layer 400 andlayer 410 as shown in FIG. 4). For example, one or more wire connections340 A, B, C, D can be positioned within the barrier layers 400, 410 ofthe shell 145 (e.g. between layer 400 and layer 410 as shown in FIG. 4).

FIG. 5 illustrates aspects of a breast implant 140 including a pluralityof sensor modules 150 A, 150 B, 150 C and 150 D. The breast implant 140depicted in FIG. 5 is shown in cross-section, a similar view as in FIGS.3 and 4. The breast implant 140 includes interior viscous material 300.The cover 155 completely surrounds and envelops the shell 145 with a gap160 between the shell 145 surface and the cover 155 surface. Projections165 traverse the gap 160 between the shell 145 and the cover 155. Theprojections define the edges of the compartments 200 A, B, C, D. Theshell 145 includes at least one barrier layer including at least onecavity, the at least one cavity configured to reversibly mate with asurface of at least one of a plurality of sensor modules. In theillustration of FIG. 5, the barrier layer is identical to the shell 145;however, in some embodiments, there is a distinct barrier layer adjacentto the interior or exterior surface of the shell 145. The shell 145includes a barrier layer with a cavity 500 A configured to reversiblymate with the surface of sensor module 150 A. Although FIG. 5 depicts agap between the surface of the cavity 500 A and the surface of thesensor module 150 A, this gap is present for illustrative purposes inthe Figure. In many embodiments, the surface of the cavity 500 A and thesurface of the sensor module 150 A would be positioned in direct contactwith each other. An adhesive or other fastener in the gap between thesurface of the cavity 500 A and the surface of the sensor module 150 Acan be included to ensure that the sensor module 150 A is securerelative to the cavity 500 A. As shown in FIG. 5, at least one surfaceof the sensor module 150 A is configured to align within thecorresponding cavity 500 A in the shell 145. Similarly, the sensormodules 150 B, 150 C and 150 D include surfaces configured to reversiblymate with the corresponding cavities 500 B, 500 C and 500 D in the shell145. Although the cavities 500 A, B, C, D illustrated in FIG. 5 are allsubstantially the same shape (i.e. rectangular), in some embodiments theshell 145 can include a plurality of cavities 500 of different sizes andshapes to correspond in size and shape to a plurality of sensor modules150.

FIG. 6 illustrates aspects of a breast implant 140 including a pluralityof sensor modules 150 A, 150 B, 150 C and 150 D. The breast implant 140depicted in FIG. 6 is shown in cross-section, a similar view as in FIGS.3, 4 and 5. The breast implant 140 includes interior viscous material300. A cover 155 completely surrounds and envelops the shell 145 with agap 160 between the shell 145 surface and the cover 155 surface. Aplurality of projections 165 extend from an external surface of theshell 145, the projections 165 forming a plurality of compartments 200A, B, C, D adjacent to the external surface of the shell 145. As shownin FIG. 6, the shell 145 includes at least one barrier layer includingat least one aperture 600, the at least one aperture 600 with a rimsurface 610 configured to reversibly mate with a surface of at least oneof the plurality of sensor modules 150. As shown in FIG. 6, at least onesurface of the sensor module 150 A is configured to align within thecorresponding rim surface 610 of an aperture 600 A in the shell 145.Similarly, the sensor modules 150 B, 150 C and 150 D include surfacesconfigured to reversibly mate with the rim surfaces 610 of thecorresponding apertures 600 B, 600 C and 600 D in the shell 145. Asillustrated in FIG. 6, the shell 145 includes an aperture 600A with rimsurface 610 configured to reversibly mate with the outer surface ofsensor module 150 A. Similarly, FIG. 6 illustrates that the shell 145includes a plurality of apertures 600 A, 600 B, 600 C, 600 D, each ofwhich include rim surfaces 610 configured to reversibly mate with theouter surface of a corresponding sensor module 150 A, 150 B, 150 C, 150D. An adhesive or other fastener can be included on the rim surface 610to ensure that a sensor module 150 is secure relative to the rim surface610 of an aperture 600. Although the apertures 600 A, B, C, Dillustrated in FIG. 6 are all substantially the same shape (i.e.rectangular), in some embodiments the shell 145 can include a pluralityof apertures 600 of different sizes and shapes to correspond in size andshape to a plurality of sensor modules 150.

As illustrated in FIGS. 5 and 6 as well as the associated text, theplurality of sensor modules 150 operably attached to the shell 145 canbe modular. The plurality of sensor modules 150 operably attached to theshell 145 can be configured to be replaceable. For example, a breastimplant 140 can include a plurality of cavities 500 in the shell 145(e.g. as shown in FIG. 5) configured to reversibly mate with the surfaceof a plurality of sensor modules 150 of different types, allowingsubstitution of different types of sensor modules 150 with specificbreast implants 140 as desired in a specific situation. For example, astandard breast implant 140 with cavities 500 of a standard size andshape can be manufactured and sensor modules 140 inserted as desired tosuit a particular medical situation. For example, a breast implant 140can include a plurality of apertures 600 in the shell 145 (e.g. as shownin FIG. 6) with rim surfaces configured to reversibly mate with thesurface of a plurality of sensor modules 150 of different types,allowing substitution of different types of sensor modules 150 withspecific breast implants 140 as desired in a specific situation. Forexample, a standard breast implant 140 with apertures 600 of a standardsize and shape can be manufactured and sensor modules 140 inserted assuitable for a particular patient. For example, sensor modules 140configured to respond to Her2/neu proteins may be included in a breastimplant 140 intended for use in a reconstructive surgery with a patientwho has a history of a Her2/neu positive breast cancer diagnosis. Forexample, sensor modules 140 configured to respond to markers of breastcancer tissue abnormalities, such as hypoxia, necrosis and inflammation,may be included in a breast implant 140 intended for use in aaugmentation surgery in a person without a history of breast cancerdiagnosis. Although FIGS. 5 and 6 do not specifically illustrate anenergy transfer unit 450, one or more energy transfer unit can beincluded, with connections to the sensor modules that are configured tobe reversible. For example, if the connection between an energy transferunit 450 and a replaceable sensor module 150 includes a wire connection340, a socket or other connection site can be included on the sensormodule 150 at a location configured to mate with the wire connection 340at a cavity 500 or aperture 600. For example, one or more energytransfer unit 450 can be positioned within an aperture. For example, oneor more energy transfer unit 450 can be positioned within a cavity. Forexample, one or more energy transfer unit 450 can be positioned adjacentto the shell 145.

FIG. 7 illustrates aspects of a sensor module 150. As illustrated inFIG. 7, the sensor module 150 includes two individual sensor units, 700,710. In some embodiments, a sensor module 150 can include a singlesensor unit or more than two sensor units. Each sensor unit 700, 710includes a sensor configured to detect at least one analyte. Each sensormodule 150 can be configured to respond to a specific analyte, or agroup of analytes. The individual sensor units 700, 710 illustrated inFIG. 7 can be configured to detect the same or different analytes,depending on the embodiment. The individual sensor units 700, 710illustrated in FIG. 7 can be configured to detect analytes of differenttypes. For example, a sensor unit 700 can be configured to detect thepresence of maspin protein in the fluid originating adjacent to theimplant 140 and a sensor unit 710 can be configured to detect thepresence of Her2/neu protein in the fluid originating adjacent to theimplant 140. In some embodiments, the sensor units 700, 710 in a sensormodule 150 can include sensor units that are configured to be activatedat different times. For example, the sensor units 700, 710 can includelong term analyte sensors, such as described in U.S. Pat. No. 7,577,470,“Long Term Analyte Sensor Array” to Shah et al., which is incorporatedherein by reference. See also European Patent Application No. 06718063.8to Shah et al., “Fabrication of Multi-Sensor Arrays,” which isincorporated herein by reference. For example, the sensor units 700, 710can include a plurality of sensors, each of which are isolated andinactive until an opening is formed in a covering over the respectivesensor, such as described in European Patent Application No. 01926347.4,“Microfabricated Devices and Methods for Storage and Selective Exposureof Chemicals,” to Santini et al., and U.S. Pat. No. 5,797,898,“Microchip Drug Delivery Devices,” to Santini et al., which are eachincorporated herein by reference. See also US Patent Application No.2011/0082356 to Yang et al., “Analyte Sensor Apparatuses HavingInterference Rejection Membranes and Methods for Making and Using Them,”which is incorporated herein by reference.

In some embodiments, a sensor unit can include a recognition element anda transducer. See, e.g. Bohunicky and Mousa, “Biosensors: The New Wavein Cancer Diagnosis,” Nanotechnology, Science and Applications, 4(2011), which is incorporated herein by reference. A recognition elementis configured to detect an analyte. In some embodiments, a recognitionelement detects an analyte through molecular binding to the analyte. Forexample, some recognition elements include proteins, antibodies,antibody fragments, aptamers, or nucleic acids that bind to specificanalytes. Recognition elements can include, for example, aptamers,molecularly imprinted polymers, antibodies, antibody mimics, or antibodysynthetics. A transducer within a sensor unit can convert a signal fromthe recognition element that an analyte has been detected to an output,such as an electrical output. In some embodiments, the transducer is anelectrochemical transducer that converts a chemical signal to anelectrical output. In some embodiments, the transducer is an opticaltransducer that converts an optical signal to an electrical output. Insome embodiments, the transducer is responsive to mass change, andconverts a mass change into an electrical signal. For example, thetransducer can include a piezoelectric element. In some embodiments, thetransducer is a calorimetric transducer that converts a thermal signalto an electrical output.

In some embodiments, a sensor module can include a processor. Forexample, a sensor module can include a micromechanical system (MEMS)device, including a microprocessor and microsensor units. In someembodiments, a sensor module can include an antenna. For example, theantenna can be configured to respond to electromagnetic energy in theradio-frequency (RF) range. In some embodiments, a sensor module caninclude an energy harvesting unit. For example, a sensor module caninclude a passive RFID energy harvesting unit. In some embodiments, asensor module can include a radio frequency identification (RFID) unit.In some embodiments, a sensor module can include a programmable RFIDdevice such as the Wireless Identification and Sensing Platform (WISP).See, for example, Sample et al., “Design of an RFID-Based Battery-FreeProgrammable Sensing Platform,” IEEE Transactions of Instrumentation andMeasurement, 57:11, 2608-2615 (2008), which is incorporated herein byreference. In some embodiments, the sensor module can include a switch.For example, the sensor module can include a switch configured to changethe state of a processor when an analyte is detected. For example, thesensor module can include a switch configured to enable a transmissionunit when an analyte is detected.

In some embodiments, a sensor module includes a plurality of reservoirs.For example, the sensor units can be operably attached to one or morereservoirs configured to provide reagent(s) required by the sensor unitsduring use. For example, the sensor units can be operably attached toone or more reservoirs configured to provide protection to the sensorunits during use. For example, the sensor units 700, 710 may be operablyattached to one or more reservoirs configured to provide protection tothe sensor units 700, 710 during use. Each of the reservoirs can includea removable cover configured to be removed prior to use of that specificreservoir. For example, each of the reservoirs can include a removablecover configured to dissolve slowly over time and thereby provide theinternal reagent(s). For example, each of the reservoirs can include aremovable cover configured to be removed by a specific signal. See, forexample, European Patent Application No. 01926347.4, “MicrofabricatedDevices and Methods for Storage and Selective Exposure of Chemicals,” toSantini et al., and U.S. Pat. No. 7,410,616, “Device for the ControlledExposure of Reservoir-Based Sensors,” to Santini et al., which are eachincorporated herein by reference. See also US Patent Application No.2011/0082356 to Yang et al., “Analyte Sensor Apparatuses HavingInterference Rejection Membranes and Methods for Making and Using Them,”which is incorporated herein by reference.

The sensor units 700, 710 in a sensor module 150 such as illustrated inFIG. 7 can include a variety of sensor types. In some embodiments, asensor module 150 includes sensor units 700, 710 of different types. Forexample, sensor unit 700 can be configured to detect an analyte (“A”)and sensor unit 710 can be configured to detect a different analyte(“B”). Sensor units 700, 710 can be selected based on the analyte(s) ofinterest in a particular embodiment. Sensor units 700, 710 can beselected based on factors such as cost, performance, durability, sizeand energy requirements. A sensor module 150 can include a recognitionelement that detects an analyte. In some embodiments, the sensor units700, 710 in a sensor module 150 can include at least one recognitionelement. In some embodiments, the sensor units 700, 710 in a sensormodule 150 can include a hydrogel-based sensor. In some embodiments, thesensor units 700, 710 in a sensor module 150 can include sensor unitsthat include crystalline colloidal array of polymer spheres polymerizedwithin a hydrogel. See, for example, Holtz and Asher, “PolymerizedColloidal Crystal Hydrogel Films as Intelligent Chemical SensingMaterials,” Nature 389: 829-832 (1997), which is incorporated herein byreference. In some embodiments, the sensor units 700, 710 in a sensormodule 150 can include sensor units that include an integrated biosensorsystem for the simultaneous detection of a plurality of different typesof targets. See, for example, U.S. Pat. No. 6,743,581, “Multifunctionaland Multispectral Biosensor Devices and Methods of Use” to Vo-Dinh,which is incorporated herein by reference. In some embodiments, thesensor units 700, 710 in a sensor module 150 can include sensor unitsthat include at least one wireless complementary metal oxidesemiconductor (CMOS) sensor. See, for example, US Patent ApplicationPublication No. 2009/0298704 to Anwar, “Wireless CMOS Biosensor,” whichis incorporated herein by reference. See also: Daniel et al.,“Implantable Diagnostic Device for Cancer Monitoring,” Biosens.Bioelectron. 24:11, 3252-3257 (2009); and Ling et al., “ImplantableMagnetic Relaxation Sensors Measure Cumulative Exposure to CardiacBiomarkers,” Nature Biotechnology 29: 3 273-278, which are eachincorporated herein by reference. In some embodiments, the sensor units700, 710 in a sensor module 150 can include sensor units that includemagnetic particles, wherein the extent of aggregation of the magneticparticles are indicative of the presence or absence of an analyte. See,for example, US Patent Application Publication No. 2010/0072994 to Leeand Berry, “NMR Systems for In Vivo Detection of Analytes,” which isincorporated herein by reference. In some embodiments, the sensor units700, 710 in a sensor module 150 can include sensor units that include ahydrogel matrix with sensor particles. See, for example, US PatentApplication Publication No. 2010/0331634 to Muller et al., “HydrogelImplant for Sensing Metabolites in Body Tissue,” which is incorporatedherein by reference. In some embodiments, the sensor units 700, 710 in asensor module 150 can include sensor units that include an optical-basedsensor including light-absorbing indicator molecules. See, for example,U.S. Pat. No. 6,304,766 to Colvin, “Optical-Based Sensing Devices,Especially for In-Situ Sensing in Humans,” which is incorporated hereinby reference. In some embodiments, the sensor units 700, 710 in a sensormodule 150 can include sensor units that include an optically readablepolydeoxy-nucleotide array with integral fluorescence excitation andfluorescence emission channels. See, for example, U.S. Pat. No.7,302,289 to Crowley, “Readable Probe Array for In-Vivo Use,” which isincorporated herein by reference. In some embodiments, a sensor unit700, 710 can be refreshed or recharged for long-term use. In someembodiments, the sensor units 700, 710 in a sensor module 150 caninclude sensor units that include a plurality of analyte bindingdomains, with each binding domain being capable of specifically andreversibly binding to at least one target analyte. See, for example,U.S. Pat. No. 7,951,605 to Pitner and Vonk, “Multianalyte Sensor,” whichis incorporated herein by reference. A sensor module can include arecognition element including at least one aptamer configured to bind toan analyte. A sensor module can include a recognition element includingat least one nucleic acid configured to bind to an analyte. A sensormodule can include a recognition element including at least one antibodyconfigured to bind to an analyte. In some embodiments, the sensor units700, 710 in a sensor module 150 can include sensor units that includematerials that produce a detectable change when the sensor unit isexposed to an analyte, such as the release of an infrared (IR)detectable dye. See, for example, U.S. Pat. No. 7,964,390 to Rozakis etal., “Sensor System,” which is incorporated herein by reference. In someembodiments, the sensor units 700, 710 in a sensor module 150 caninclude sensor units that include graphene-based nanosensors. See, forexample, Mannoor et al., “Graphene-based Wireless Bacteria Detection onTooth Enamel,” Nature Communications, 3:763 doi: 10.1038/ncomms1767(2012).

In some embodiments, the sensor units 700, 710 in a sensor module 150can include sensor units utilizing recognition elements that are nucleicacid ligands, such as aptamers, configured to bind to specific targetproteins that are analytes. In some embodiments, aptamers can berecognition elements for specific analytes. In some embodiments,aptamers specific to particular analytes can be generated using an invitro selection process referred to as SELEX (Systematic Evolution ofLigands by Exponential enrichment). See, for example U.S. Pat. No.5,475,096, “Nucleic Acid Ligands,” to Gold et al., and U.S. Pat. No.5,270,163, “Methods for Identifying Nucleic Acid Ligands,” to Gold etal., which are each incorporated herein by reference. In someembodiments, one or more sensor units include chemiresistors withaptamers. Aptamers can be thiol-functionalized during fabrication of achemiresistor with aptamers configured as functional elements.Thiol-functionalized binding aptamers can be obtained from commercialsources such as Integrated DNA Technology, Inc. (Coralville, Iowa).Examples of a thiol-functionalized aptamers for breast cancer analytescan be found, for example, in Da Pieve et al., “Development of Anti-MUC1DNA Aptamers for the Imaging of Breast Cancer,” Breast Cancer Res,10(Suppl 2):P62, (2008), which is incorporated herein by reference. Thechemoresistor sensor units carrying recognition elements can beconfigured, for example, to detect analytes that are proteins or proteinfragments, such as MUC 1 protein, Her2 protein, or PDGF-AA protein (see,e.g., Chourb et al., “Enhanced Immuno-Detection of Shed ExtracellularDomain of Her-2/Neu,” Sci. Res. 1:4, 325-329 (2009), which isincorporated herein by reference).

As shown in FIG. 7, a sensor module 150 can include a structural region730. The structural region 730 can be fabricated from a variety ofmaterials, depending on the embodiment. For example, the structuralregion 730 can be fabricated from a polymer, a silicone-based material,a fabric, or a resin. The structural region 730 can be fabricated fromflexible materials, or configured for flexibility. The structural region730 can be fabricated to be bio-compatible. The structural region 730can be fabricated to be small and lightweight to minimize added weighton the shell 145 from the sensor modules 150. The structural region 730can include a base or support for various portions of the sensor module150. The structural region 730 can include adhesive to affix the sensormodule 150 to the surface of a shell of a breast implant. The structuralregion 730 can include one or more surfaces configured to reversiblymate with a surface of a cavity in a barrier layer in a shell of abreast implant. The structural region 730 can include one or moreapertures. The structural region 730 can include an outer shell or coverover the entirety or a part of the various portions of the sensor module150. For example, the structural region 730 can include one or moreareas configured to allow analytes to flow from the tissue fluidadjacent to the breast implant into the sensor module 150, such asillustrated as regions 750 and 760 in FIG. 7. For example, one or moreareas of the structural region 730 configured to allow analytes to flowfrom the tissue fluid adjacent to the breast implant into the sensormodule 150 can include one or more mesh-like or porous regions. Forexample, the structural region 730 can include a region of filmconfigured with microchannels to direct fluid from the adjacent tissueto a position adjacent to the sensor units 700, 710. See, for example,U.S. Pat. No. 6,420,622 “Medical Article Having Fluid Control Film,” toJohnston et al., which is incorporated herein by reference. For example,the structural region 730 can include a polymeric cover. For example,the structural region 730 can include a cover that can be opened inresponse to a specific signal, such as described in European PatentApplication No. 01926347.4, “Microfabricated Devices and Methods forStorage and Selective Exposure of Chemicals,” to Santini et al., whichis incorporated herein by reference. For example, the structural region730 can include a surface configured to interface with a surface of acover 155 (not shown in FIG. 7).

The sensor module 150 shown in FIG. 7 includes a unique identifier, 720.A unique identifier is configured to identify a particular sensor module150 from any other sensor modules 150 attached to a shell of aparticular breast implant. For example, a unique identifier can includean alphanumeric code. For example, a unique identifier can include apositional identifier. For example, a unique identifier can include anelectronic code, such as a radio frequency identification (RFID)identifier code. For example, a unique identifier can include anelectronic code, such as a binary-based code.

A sensor module 150 can include an energy harvesting unit 440. Forexample, an energy harvesting unit can be a passive RFID energyharvesting unit. For example, an energy harvesting unit can be aphotovoltaic cell configured for subcutaneous use. A sensor module 150can include an antenna 420. A sensor module 150 can include a switch.For an example of a switch that can be connected to a sensor, see U.S.Pat. No. 7,411,505 “Switch Status and RFID Tag” to Smith, which isincorporated herein by reference. For example, a switch can be operablypositioned between a sensor unit 700, 710 and an antenna 420, andconfigured to allow a signal to be transmitted from the antenna 420 onlywhen the switch is in a permissive state. In some embodiments, a sensormodule 150 includes a switch configured to activate a processor. Forexample, a sensor module 150 can include a switch controlling aprocessor, so that the processor is activated when the sensor moduledetects an analyte. In some embodiments, a sensor module 150 includes aswitch configured to activate a transmission unit. For example, a sensormodule 150 can include a switch controlling a transmission unit, so thatthe transmission unit initiates a signal when the sensor module detectsan analyte.

FIG. 8 illustrates additional aspects of an embodiment of a breastimplant 140. The breast implant 140 depicted in FIG. 8 is shown in anex-vivo exterior view. The breast implant 140 includes interior viscousmaterial 300. A cover 155 completely surrounds and envelops the shell145 with a gap 160 between the surface of the shell 145 and the surfaceof the cover 155. For the purposes of illustration, the cover 155 isshown in a cross-section view around the shell 145 surface. A pluralityof projections 165 extend from an external surface of the shell 145, theprojections 165 forming a plurality of compartments 200 A, B, C, Dadjacent to the external surface of the shell 145. Each of thecompartments 200 A, B, C, D includes a sensor module 150 A, B, C, D.FIG. 8 shows a breast implant 140 including shell 145 and a plurality ofsensor modules 150 A, B, C, D attached to the exterior of the shell 145.Each of the sensor modules 150 A, B, C, D attached to the exterior ofthe shell 145 are oriented to detect one or more analytes in a fluidadjacent to the shell. Each of the sensor modules 150 A, B, C, Dattached to the exterior of the shell 145 includes a unique identifier(not illustrated in FIG. 8). Also attached to the exterior of the shell145 is a optically powered transducer 800 configured to harvest opticalenergy from a source external to the breast implant. For example, theoptically powered transducer 800 can include a photovoltaic cellconfigured for subcutaneous use. See, for example, US Patent PublicationNo. 2011/0044694 to Scherer et al., “Systems and Methods for OpticallyPowering Transducers and Related Transducers,” which is incorporatedherein by reference. See also Ayazian and Hassibi, “Delivering OpticalPower to Subcutaneous Implanted Devices,” 33^(rd) Annual InternationalConference of the IEEE EMBS, Boston Mass. Aug. 30- Sep. 3, 2011, pages2874-2877, which is incorporated herein by reference. In the illustratedembodiment, the cover 155 is transparent to the wavelength, or range ofwavelengths, of optical waves utilized by the optically poweredtransducer 800. In some embodiments, the optically powered transducer800 is positioned to align with a corresponding aperture in the cover155. In some embodiments, the optically powered transducer 800 ispositioned with the relevant portions on an external face of the cover155. For example, the optically powered transducer 800 can be positionedwithin a corresponding aperture of the cover 155. A wire connector 810is positioned to transmit the power harvested by the optically poweredtransducer 800 to each of the sensor modules 150 A, B, C, D attached tothe exterior of the shell 145. Although the wire connector 810 isillustrated in FIG. 8 as external to the shell 145, in some embodimentsthe wire connector 810 may be positioned internally to the shell 145.

FIG. 8 illustrates an embodiment of a breast implant 140 including aoptically powered transducer 800 ex-vivo. The optically poweredtransducer 800 is positioned on the shell 145 in a position to allow foroptical waves (i.e. light) to transmit through the breast tissue to theoptically powered transducer 800. In some embodiments, the opticallypowered transducer 800 is positioned on an external surface of the cover155. In some embodiments, the optically powered transducer 800 ispositioned on an external surface of the shell 145 in a positionadjacent to a corresponding aperture or set of apertures, in the cover155. An appropriate position of the optically powered transducer 800depends on the size and shape of a particular breast implant 140 and itsintended position within the tissue of a particular patient. Forexample, it can be desirable to position the optically poweredtransducer 800 at a location on the surface of the breast implant 140that is likely to have minimal tissue between the surface of theoptically powered transducer 800 and the external surface of thepatient's skin. For example, it can be desirable to position theoptically powered transducer 800 at a location on the surface of thebreast implant 140 that will be adjacent to the underside of the breastin vivo (e.g. adjacent to a location such as the one labeled 114 in FIG.1). The specific configuration of the optically powered transducer 800can be selected based on the expected tissue thickness and compositionthat the light will travel through to reach the optically poweredtransducer 800. See, for example, Ayazian and Hassibi, “DeliveringOptical Power to Subcutaneous Implanted Devices,” 33^(rd) AnnualInternational Conference of the IEEE EMBS, Boston Mass. Aug. 30- Sep. 3,2011, pages 2874-2877, which is incorporated herein by reference. Forexample, it can be undesirable to position the optically poweredtransducer 800 at a location on the surface of the breast implant 140that will be adjacent to the chest wall in vivo (e.g. adjacent to alocation such as the ones labeled 122, 120 and 124 in FIG. 1). A breastimplant 140 including an optically powered transducer 800 can be poweredwith a light source placed adjacent to the skin at times to be desiredfor routine screening, for example during regular medical office visits.At other times, the sensor system of the breast implant 140 can be leftdormant or minimally powered.

In some embodiments, a breast implant 140 including an optically poweredtransducer 800 can be configured to be compatible with magneticresonance imaging (MRI) screening for breast cancer and related tissuechanges. For example, a breast implant 140 including an opticallypowered transducer 800 can be fabricated without ferromagneticmaterials. A breast implant 140 including an optically poweredtransducer 800 fabricated without ferromagnetic materials can include asilicon-based complementary metal-oxide-semiconductor (CMOS) basedoptically powered transducer 800 as well as sensor modules 150fabricated without ferromagnetic materials. See, for example, Ayazianand Hassibi, “Delivering Optical Power to Subcutaneous ImplantedDevices,” 33^(rd) Annual International Conference of the IEEE EMBS,Boston Mass. Aug. 30- Sep. 3, 2011, pages 2874-2877, which isincorporated herein by reference. A breast implant 140 including anoptically powered transducer 800 fabricated without ferromagneticmaterials can also be desirable for use with routine mammographicscreening to minimize scatter on the resulting mammogram image.

FIG. 9 illustrates aspects of a breast implant 140 in use. FIG. 9depicts a cross-section view of the breast implant 140 in situ within abreast 100. The view of the breast implant 140 in vivo is similar to theview depicted in FIG. 1. FIG. 9 shows a cross-section view through theside of an individual person, including a cross-section view of theindividual's ribs 130 in the chest wall 122, 120, 124. A fluid-permeablecover 155 completely surrounds and envelops the shell 145 with a gap 160between the shell 145 surface and the cover 155 surface. A plurality ofprojections 165 extend from an external surface of the shell 145, theprojections 165 forming a plurality of compartments 200 A, B, C, D, E,F, G adjacent to the external surface of the shell 145. Each of thecompartments 200 A, B, C, D, E, F, G includes a sensor module 150 A, B,C, D, E, F, G. The breast implant 140 includes a plurality of sensormodules 150 A, B, C, D, E, F and G. Each of the sensor modules 150 A, B,C, D, E, F and G is attached to the shell 145 and oriented to detect oneor more analytes in a fluid adjacent to the shell 145. A cover 155completely surrounds and envelops the shell 145, with a gap 160 betweenthe surface of the shell 145 and the surface of the cover 155. An energytransfer unit 450 including an antenna 420 and an energy harvesting unit440 are attached to the surface of the shell 145 of the breast implant140. Although for the purposes of illustration, connections are notexplicitly shown between the energy transfer unit 450 and the sensormodules 150 A, B, C, D, E, F and G, such connections are present in theillustrated embodiment. Information regarding the status of the sensorsis conveyed from the individual sensor modules 150 A, B, C, D, E, F andG to the energy transfer unit 450 through connections, such as wireconnections (not illustrated in FIG. 9, but see FIG. 4). The energytransfer unit 450 then causes a signal 910 to be sent from the antenna420 to a remote device 920. In some embodiments, the energy transferunit 450 can be a passive RFID device, wherein a signal 900 originatingfrom the remote device 920 provides the energy to transmit thecorresponding signal 910 from the implant 140.

In some embodiments, the energy transfer unit 450 can operate as atransmission unit. A “transmission unit,” as used herein, is a unit thatfunctions to transmit a signal out of the implant region to a regionexternal from the individual carrying the implant. A energy transferunit 450 can be configured to transmit a signal in response to aninterrogation signal. For example, an energy transfer unit 450 can beconfigured to transmit a signal after receiving an interrogation signaloriginating from a remote device. An energy transfer unit 450 caninclude a transponder utilizing electromagnetic waves, for example asdescribed in “Fundamental Operating Principles,” in Chapter 3 of theRFID Handbook: Fundamentals and Applications in Contactless Smart Cardsand Identification, Klaus Finkenzeller, John Wiley & Sons, (2003), whichis incorporated herein by reference. An energy transfer unit 450 caninclude an oscillator and encoder configured to generate a programmablepulse position-modulated signal in the radio frequency range. See, forexample, U.S. Pat. No. 4,384,288 to Walton, titled “Portable RadioFrequency Emitting Identifier,” which is incorporated herein byreference. An energy transfer unit 450 can include a radio frequencyidentification device (RFID). An energy transfer unit 450 can beconfigured to be a transmitter of signals in the UHF range. An energytransfer unit 450 including an RFID device can be configured to transmitsignals in the UHF standard range utilized in a global region, asillustrated in the “Worldwide RFID UHF Map” by Intelleflex Corporation(©2009), which is incorporated herein by reference. An energy transferunit 450 can include a radio frequency identification device (RFID),which can be a passive RFID device, or a semi-passive RFID device,depending on the embodiment. See, for example, Chawla and Ha, “AnOverview of Passive RFID,” IEEE Applications and Practice, 11-17(September 2007), which is incorporated herein by reference. An energytransfer unit 450 can include an optical transmitter unit. An energytransfer unit 450 can be configured to transmit at approximately 13.56megahertz (MHz), or within the ISO 14443 standard parameters. SeePatauner et al., “High Speed RFID/NFC at the Frequency of 13.56 MHz,”presented at the First International EURASIP Workshop on RFIDTechnology, pages 1-4, 24-25 Sep. 2007, Vienna Austria, which isincorporated herein by reference. An energy transfer unit 450 caninclude a hybrid backscatter system configured to function in an RFID,IEEE 802.11x standard and Bluetooth system. See, for example, U.S. Pat.No. 7,215,976 to Brideglall, titled “RFID Device, System and Method ofOperation Including a Hybrid backscatter-based RFID Protocol Compatiblewith RFID, Bluetooth and/or IEEE 802.11x Infrastructure,” which isincorporated herein by reference. An energy transfer unit 450 caninclude a near field communication (NFC) device. An energy transfer unit450 can include a Wireless Identification and Sensing Platform (WISP)device, manufactured by Intel Corporation, such as described in the“WISP: Wireless Identification and Sensing Platform” webpage (downloadedon Oct. 28, 2011) incorporated herein by reference. An energy transferunit 450 can include an infrared (IR) source (approximately 0.74 μm to300 μm in wavelength). An energy transfer unit 450 can include a lightsource in the visible wavelengths (approximately 380 nm to 740 nm inwavelength).

A user 930, such as a medical professional, operates the remote device920. Although user 930 is shown/described herein as a single illustratedfigure, user 930 can be representative of a human user, a robotic user(e.g., computational entity), and/or substantially any combinationthereof (e.g., a user can be assisted by one or more robotic agents)unless context dictates otherwise. In general, the same may be said of“sender” and/or other entity-oriented terms as such terms are usedherein unless context dictates otherwise.

The remote device 920 can be integrated into a multifunctional device,such as a cell phone, medical scanner, nursing personal digitalassistant (PDA), or other device. In some embodiments, the remote device920 is integrated into a piece of medical equipment, such as a medicalmonitor device. In some embodiments, the remote device 920 is astand-alone device. The remote device 920 can include an indicator unit950, such as a display, touchscreen, light indicator, auditoryindicator, vibration emitter, or similar units. The remote device 920can include a user interface 940 such as a keyboard, one or morebuttons, a touchscreen, or similar units. The remote device 920 caninclude a transmitter configured to transmit signals 900 configured tobe received by the breast implant 140. For example, signals 900transmitted from the remote device 920 can be configured to be receivedby the antenna 420. In some embodiments, the signal 900 may be aradio-frequency wave, an IR wave, or ultrasound.

Although the remote device 920 is illustrated in FIG. 9 as a distanceaway from the surface of the breast 100, in some embodiments the remotedevice 920 may have an operational range that is no more thanapproximately 5-10 cm in linear distance. Therefore, in some embodimentsthe remote device 920 can be placed in contact with the surface of thebreast 100, or in close proximity to the breast 100 (i.e. no more than10 cm away from the surface), during use. For example, in someembodiments the remote device 920 can be configured to transmit lighttransdermally to the breast implant 140, and the remote device 920 maybe placed in contact with the skin surface in a desired location foroptimal transdermal transmission.

FIG. 10 illustrates aspects of a remote device 920. The remote device920 is configured to receive signals 910 from a breast implant in situ(not depicted). The remote device 920 is operated by a user 930, such asa medical professional. The remote device 920 includes an indicator unit950 that is a display. The remote device 920 includes a user interface940 that is a keyboard. The remote device 920 includes circuitry 1000configured for receiving information from a breast implant. For example,the remote device 920 can include a receiver. For example, the remotedevice 920 can include an antenna. For example, the remote device 920can include a processor. For example, the remote device 920 can includenon-volatile memory. For example, the remote device 920 can includelogic. For example, the remote device 920 can include instructions foroperations relating to monitoring information from a breast implant. Forexample, the remote device 920 can include look-up tables and otherstored information that can be associated with a stored signal, such asthe relative location on a breast implant for the sensor moduleassociated with each specific identification code.

FIG. 11 depicts a sensor module 150. In the illustrated embodiment, acircuitry region 1100 of the sensor module 150 is printed on to thesurface of a breast implant (as described in Example 1, below). Thecircuitry region 1100 includes an RFID unit 1110, including an antenna420 and an identification code 1130 specific for the sensor module 150.The circuitry region 1100 includes an antenna 420. The sensor module 150also includes an array 1120 of sensor units 700. Although sensor units700 are all depicted similarly, they can include sensors configured toidentify different analytes (see Example 1). Each sensor unit 700 in thearray 1120 is part of a set 1130, 1135, 1140, 1145, 1150, 1155, 1160,1165, 1170, 1175, 1180, 1185. As shown in FIG. 11, each set 1130, 1135,1140, 1145, 1150, 1155, 1160, 1165, 1170, 1175, 1180, 1185 of sensorunits 700 in the array includes 7 sensor units 700. Each of the sets set1130, 1135, 1140, 1145, 1150, 1155, 1160, 1165, 1170, 1175, 1180, 1185can include its own cover (not illustrated). Each cover can befabricated so as to be disrupted when electrical current is appliedacross the cover (see e.g., U.S. Pat. No. 7,577,470, “Long Term AnalyteSensor Array” to Shah et al., which is incorporated herein byreference). Each cover can be operably connected to the RFID unit 1110,for example through a wire connection (not illustrated).

In some embodiments, a breast implant includes: a shell configured to besubstantially filled with a viscous material; a plurality of projectionsextending from an external surface of the shell, the plurality ofprojections forming a plurality of compartments adjacent to the externalsurface of the shell; a plurality of sensor modules attached to theshell, each of the sensor modules configured to detect one or morebiological analytes arising from biological tissue, the fluid within oneof the plurality of compartments; at least one antenna; an energyharvesting unit attached to the at least one antenna; and at least oneconnection between the energy harvesting unit and each of the pluralityof sensor modules. In some embodiments, the breast implant includes aplurality of sensor modules attached to the shell, wherein the pluralityof sensor modules are positioned on the shell with a distance betweenthe sensor modules. In some embodiments, the breast implant includes atleast one switch attached to both the at least one transmission unit andthe plurality of sensor modules, the at least one switch configured toactivate the transmission unit in response to a signal from one or moreof the sensor modules.

A method of monitoring information from a breast implant, such as thosedescribed herein, includes: receiving first information from a firstsensor module attached to a shell of a breast implant within anindividual, wherein the first information includes a first unique sensormodule identifier and sensor data from the first sensor module;receiving second information from a second sensor module attached to theshell of the breast implant within the individual, wherein the secondinformation includes a second unique sensor module identifier and sensordata from the second sensor module; forming an initial record from thefirst information and the second information; calculating deviationlimits regarding the initial record; setting deviation parameters basedon the deviation limits and a predetermined set of standards; saving theinitial record and the deviation parameters in memory in a computingdevice; receiving third information from the first sensor moduleattached to the shell of the breast implant within the individual,wherein the third information includes the first unique sensor moduleidentifier and sensor data from the first sensor module; receivingfourth information from the second sensor module attached to the shellof the breast implant within the individual, wherein the fourthinformation includes the second unique sensor module identifier andsensor data from the second sensor module; updating the initial recordwith the third information and the fourth information; saving theupdated record in memory in the computing device; comparing the updatedrecord to the initial record and to the deviation parameters; andindicating if the updated record is within the deviation parameters ofthe initial record. Some embodiments of the method of monitoringinformation from a breast implant include: receiving fifth informationfrom the first sensor module attached to the shell of the breast implantwithin the individual, wherein the fifth information includes the firstunique sensor module identifier and sensor data from the first sensormodule; receiving sixth information from the second sensor moduleattached to the shell of the breast implant within the individual,wherein the sixth information includes the second unique sensor moduleidentifier and sensor data from the second sensor module; updating theinitial record with the fifth information and the sixth information;saving the updated record in memory in the computing device; comparingthe updated record to the initial record and to the deviationparameters; and indicating if the updated record is within the deviationparameters of the initial record. This method can be carried out, forexample, by a remote device. In some embodiments, the deviationparameters include no information or insufficient information from atleast one sensor module.

In some embodiments, a method of monitoring information from a breastimplant includes: sending a signal from a transmission unit attached toone or more sensor modules attached to a breast implant in vivo, whereinthe signal contains information regarding the detection of one or morebiological analytes by the one or more sensor modules. The signal can bereceived, for example, by a remote device. Information regarding thereceived signal can be processed, for example, by a remote device or bya remote computing device. A display including at least a portion of theprocessed information can be initiated by the remote device. A displayincluding at least a portion of the processed information can beinitiated by the remote device. The signal can be saved in memory in aremote device or in a remote device. Processed information regarding thesignal can be saved in memory in a remote device or in a remote device.In some embodiments, a detection result for each of the one or moresensor modules includes a positive result, a negative result, or a nullresult. For example, a positive result can indicate the detection of ananalyte by a specific sensor module. For example, a negative result canindicate no detection of an analyte by a specific sensor module. Forexample, a null result can indicate no information, or insufficientinformation, regarding detection of an analyte by a specific sensormodule.

In some embodiments, a method of monitoring information from a breastimplant includes: sending, from a remote device, a query signal to atleast one transmission unit attached to a breast implant in vivo, the atleast one transmission unit attached to one or more sensor modulesconfigured to detect biological analytes in fluid from biologicaltissue; receiving, from a remote device, a response signal from the atleast one transmission unit attached to the breast implant, the responsesignal including information from the one or more sensor modules;processing, in a computing device, the response signal to identifyinformation from the one or more sensor modules; and identifying, foreach of the one or more sensor modules, a detection result and a uniqueidentifier. In some embodiments, the detection result for each of theone or more sensor modules includes a positive result, a negativeresult, or a null result. For example, a positive result can indicatethe detection of an analyte by a specific sensor module. For example, anegative result can indicate no detection of an analyte by a specificsensor module. For example, a null result can indicate no information,or insufficient information, regarding detection of an analyte by aspecific sensor module. Some embodiments include initiating a display ofthe detection result and the unique identifier for at least one of thesensor modules. For example, initiating a display can include initiatinga display on a computer screen or touchpad. For example, initiating adisplay can include initiating a printout. Some embodiments includeinitiating a graphic display of the breast implant, the graphic displayincluding a position for each of the sensor modules and the detectionresult for at least one of the sensor modules. For example, initiating agraphic display of the breast implant can include initiating a diagramor illustration of the breast implant on a computer screen, the graphicdisplay including representations of the sensor modules, and thedetection result for at least one of the sensor modules. For example,initiating a graphic display of the breast implant can includeinitiating a diagram or illustration of the breast implant created as acomputer printout. Some embodiments include saving at least one resultin a remote device or a remote computing device. Some embodimentsinclude saving, for each of the one or more sensor modules, a detectionresult in a remote device or a remote computing device. Some embodimentsinclude saving the response signal in a remote device or a remotecomputing device.

The state of the art has progressed to the point where there is littledistinction left between hardware, software, and/or firmwareimplementations of aspects of systems; the use of hardware, software,and/or firmware is generally (but not always, in that in certaincontexts the choice between hardware and software can becomesignificant) a design choice representing cost vs. efficiency tradeoffs.There are various vehicles by which processes and/or systems and/orother technologies described herein can be effected (e.g., hardware,software, and/or firmware), and the preferred vehicle will vary with thecontext in which the processes and/or systems and/or other technologiesare deployed. For example, if an implementer determines that speed andaccuracy are paramount, the implementer may opt for a mainly hardwareand/or firmware vehicle; alternatively, if flexibility is paramount, theimplementer may opt for a mainly software implementation; or, yet againalternatively, the implementer may opt for some combination of hardware,software, and/or firmware. Hence, there are several possible vehicles bywhich the processes and/or devices and/or other technologies describedherein may be effected, none of which is inherently superior to theother in that any vehicle to be utilized is a choice dependent upon thecontext in which the vehicle will be deployed and the specific concerns(e.g., speed, flexibility, or predictability) of the implementer, any ofwhich may vary. Optical aspects of implementations will typically employoptically-oriented hardware, software, and or firmware.

In some implementations described herein, logic and similarimplementations may include software or other control structures.Electronic circuitry, for example, may have one or more paths ofelectrical current constructed and arranged to implement variousfunctions as described herein. In some implementations, one or moremedia may be configured to bear a device-detectable implementation whensuch media hold or transmit device detectable instructions operable toperform as described herein. In some variants, for example,implementations may include an update or modification of existingsoftware or firmware, or of gate arrays or programmable hardware, suchas by performing a reception of or a transmission of one or moreinstructions in relation to one or more operations described herein.Alternatively or additionally, in some variants, an implementation mayinclude special-purpose hardware, software, firmware components, and/orgeneral-purpose components executing or otherwise invokingspecial-purpose components. Specifications or other implementations maybe transmitted by one or more instances of tangible transmission mediaas described herein, optionally by packet transmission or otherwise bypassing through distributed media at various times.

Alternatively or additionally, implementations may include executing aspecial-purpose instruction sequence or invoking circuitry for enabling,triggering, coordinating, requesting, or otherwise causing one or moreoccurrences of virtually any functional operations described herein. Insome variants, operational or other logical descriptions herein may beexpressed as source code and compiled or otherwise invoked as anexecutable instruction sequence. In some contexts, for example,implementations may be provided, in whole or in part, by source code,such as C++, or other code sequences. In other implementations, sourceor other code implementation, using commercially available and/ortechniques in the art, may be compiled, implemented, translated, and/orconverted into a high-level descriptor language (e.g., initiallyimplementing described technologies in C or C++ programming language andthereafter converting the programming language implementation into alogic-synthesizable language implementation, a hardware descriptionlanguage implementation, a hardware design simulation implementation,and/or other such similar mode(s) of expression). For example, some orall of a logical expression (e.g., computer programming languageimplementation) may be manifested as a Verilog-type hardware description(e.g., via Hardware Description Language (HDL) and/or Very High SpeedIntegrated Circuit Hardware Descriptor Language (VHDL)) or othercircuitry model which may then be used to create a physicalimplementation having hardware (e.g., an Application Specific IntegratedCircuit). Those skilled in the art will recognize how to obtain,configure, and optimize suitable transmission or computational elements,material supplies, actuators, or other structures in light of theseteachings.

The foregoing detailed description has set forth various embodiments ofthe devices and/or processes via the use of block diagrams, flowcharts,and/or examples. Insofar as such block diagrams, flowcharts, and/orexamples contain one or more functions and/or operations, each functionand/or operation within such block diagrams, flowcharts, or examples canbe implemented, individually and/or collectively, by a wide range ofhardware, software, firmware, or virtually any combination thereof. Inone embodiment, several portions of the subject matter described hereinmay be implemented via Application Specific Integrated Circuits (ASICs),Field Programmable Gate Arrays (FPGAs), digital signal processors(DSPs), or other integrated formats. However, some aspects of theembodiments disclosed herein, in whole or in part, can be equivalentlyimplemented in integrated circuits, as one or more computer programsrunning on one or more computers (e.g., as one or more programs runningon one or more computer systems), as one or more programs running on oneor more processors (e.g., as one or more programs running on one or moremicroprocessors), as firmware, or as virtually any combination thereof,and that designing the circuitry and/or writing the code for thesoftware and or firmware would be well within the skill of one of skillin the art in light of this disclosure. In addition, the mechanisms ofthe subject matter described herein are capable of being distributed asa program product in a variety of forms, and that an illustrativeembodiment of the subject matter described herein applies regardless ofthe particular type of signal bearing medium used to actually carry outthe distribution. Examples of a signal bearing medium include, but arenot limited to, the following: a recordable type medium such as a floppydisk, a hard disk drive, a Compact Disc (CD), a Digital Video Disk(DVD), a digital tape, a computer memory, etc.; and a transmission typemedium such as a digital and/or an analog communication medium (e.g., afiber optic cable, a waveguide, a wired communications link, a wirelesscommunication link (e.g., transmitter, receiver, transmission logic,reception logic, etc.), etc.).

In a general sense, those skilled in the art will recognize that thevarious aspects described herein which can be implemented, individuallyand/or collectively, by a wide range of hardware, software, firmware,and/or any combination thereof can be viewed as being composed ofvarious types of “electrical circuitry.” Consequently, as used herein,“electrical circuitry” includes, but is not limited to, electricalcircuitry having at least one discrete electrical circuit, electricalcircuitry having at least one integrated circuit, electrical circuitryhaving at least one application specific integrated circuit, electricalcircuitry forming a general purpose computing device configured by acomputer program (e.g., a general purpose computer configured by acomputer program which at least partially carries out processes and/ordevices described herein, or a microprocessor configured by a computerprogram which at least partially carries out processes and/or devicesdescribed herein), electrical circuitry forming a memory device (e.g.,forms of memory (e.g., random access, flash, read only, etc.)), and/orelectrical circuitry forming a communications device (e.g., a modem,communications switch, optical-electrical equipment, etc.). The subjectmatter described herein may be implemented in an analog or digitalfashion or some combination thereof.

At least a portion of the devices and/or processes described herein canbe integrated into an image processing system. A typical imageprocessing system generally includes one or more of a system unithousing, a video display device, memory such as volatile or non-volatilememory, processors such as microprocessors or digital signal processors,computational entities such as operating systems, drivers, applicationsprograms, one or more interaction devices (e.g., a touch pad, a touchscreen, an antenna, etc.), control systems including feedback loops andcontrol motors (e.g., feedback for sensing lens position and/orvelocity; control motors for moving/distorting lenses to give desiredfocuses). An image processing system may be implemented utilizingsuitable commercially available components, such as those typicallyfound in digital still systems and/or digital motion systems.

At least a portion of the devices and/or processes described herein canbe integrated into a data processing system. A data processing systemgenerally includes one or more of a system unit housing, a video displaydevice, memory such as volatile or non-volatile memory, processors suchas microprocessors or digital signal processors, computational entitiessuch as operating systems, drivers, graphical user interfaces, andapplications programs, one or more interaction devices (e.g., a touchpad, a touch screen, an antenna, etc.), and/or control systems includingfeedback loops and control motors (e.g., feedback for sensing positionand/or velocity; control motors for moving and/or adjusting componentsand/or quantities). A data processing system may be implementedutilizing suitable commercially available components, such as thosetypically found in data computing/communication and/or networkcomputing/communication systems.

The herein described components (e.g., operations), devices, objects,and the discussion accompanying them are used as examples for the sakeof conceptual clarity and that various configuration modifications arecontemplated. Consequently, as used herein, the specific exemplars setforth and the accompanying discussion are intended to be representativeof their more general classes. In general, use of any specific exemplaris intended to be representative of its class, and the non-inclusion ofspecific components (e.g., operations), devices, and objects should notbe taken limiting.

The herein described subject matter sometimes illustrates differentcomponents contained within, or connected with, different othercomponents. It is to be understood that such depicted architectures aremerely exemplary, and that in fact many other architectures may beimplemented which achieve the same functionality. In a conceptual sense,any arrangement of components to achieve the same functionality iseffectively “associated” such that the desired functionality isachieved. Hence, any two components herein combined to achieve aparticular functionality can be seen as “associated with” each othersuch that the desired functionality is achieved, irrespective ofarchitectures or intermedial components. Likewise, any two components soassociated can also be viewed as being “operably connected”, or“operably coupled,” to each other to achieve the desired functionality,and any two components capable of being so associated can also be viewedas being “operably couplable,” to each other to achieve the desiredfunctionality. Specific examples of operably couplable include but arenot limited to physically mateable and/or physically interactingcomponents, and/or wirelessly interactable, and/or wirelesslyinteracting components, and/or logically interacting, and/or logicallyinteractable components.

In some instances, one or more components may be referred to herein as“configured to,” “configured by,” “configurable to,” “operable/operativeto,” “adapted/adaptable,” “able to,” “conformable/conformed to,” etc.Such terms (e.g. “configured to”) can generally encompass active-statecomponents and/or inactive-state components and/or standby-statecomponents, unless context requires otherwise.

While particular aspects of the present subject matter described hereinhave been shown and described, it will be apparent that, based upon theteachings herein, changes and modifications may be made withoutdeparting from the subject matter described herein and its broaderaspects and, therefore, the appended claims are to encompass withintheir scope all such changes and modifications as are within the truespirit and scope of the subject matter described herein. In general,terms used herein, and especially in the appended claims (e.g., bodiesof the appended claims) are generally intended as “open” terms (e.g.,the term “including” should be interpreted as “including but not limitedto,” the term “having” should be interpreted as “having at least,” theterm “includes” should be interpreted as “includes but is not limitedto,” etc.). If a specific number of an introduced claim recitation isintended, such an intent will be explicitly recited in the claim, and inthe absence of such recitation no such intent is present. For example,as an aid to understanding, the following appended claims may containusage of the introductory phrases “at least one” and “one or more” tointroduce claim recitations. However, the use of such phrases should notbe construed to imply that the introduction of a claim recitation by theindefinite articles “a” or “an” limits any particular claim containingsuch introduced claim recitation to claims containing only one suchrecitation, even when the same claim includes the introductory phrases“one or more” or “at least one” and indefinite articles such as “a” or“an” (e.g., “a” and/or “an” should typically be interpreted to mean “atleast one” or “one or more”); the same holds true for the use ofdefinite articles used to introduce claim recitations. In addition, evenif a specific number of an introduced claim recitation is explicitlyrecited, such recitation should typically be interpreted to mean atleast the recited number (e.g., the bare recitation of “tworecitations,” without other modifiers, typically means at least tworecitations, or two or more recitations). Furthermore, in thoseinstances where a convention analogous to “at least one of A, B, and C,etc.” is used, in general such a construction is intended in the senseone having skill in the art would understand the convention (e.g., “asystem having at least one of A, B, and C” would include but not belimited to systems that have A alone, B alone, C alone, A and Btogether, A and C together, B and C together, and/or A, B, and Ctogether, etc.). In those instances where a convention analogous to “atleast one of A, B, or C, etc.” is used, in general such a constructionis intended in the sense one would understand the convention (e.g., “asystem having at least one of A, B, or C” would include but not belimited to systems that have A alone, B alone, C alone, A and Btogether, A and C together, B and C together, and/or A, B, and Ctogether, etc.). Typically a disjunctive word and/or phrase presentingtwo or more alternative terms, whether in the description, claims, ordrawings, should be understood to contemplate the possibilities ofincluding one of the terms, either of the terms, or both terms unlesscontext dictates otherwise. For example, the phrase “A or B” will betypically understood to include the possibilities of “A” or “B” or “Aand B.”

EXAMPLES Example 1 A Breast Implant System Constructed with Ink-JetPrinting and Including Multiple Sensor Modules

A patient has a total reconstruction of the breast employing a breastimplant system. The breast implant system includes a gel-filled breastimplant prostheses containing multiple long-lived sensor modules tomonitor the tissues surrounding the implant for any new or recurrentbreast cancers that may arise. The long-lived sensor modules detectanalytes that are breast cancer markers and include a power source, atransmitter, and an identification code for each sensor module. Theimplant system also includes an external, remote device with a receiveroperable to receive transmissions from the sensor modules and to alertthe patient and medical personnel if breast cancer markers are detected.

The breast implant prosthesis is a gel-filled hemispherical orcrescent-shaped implant with a shell. The implant includes, on thesurface of the shell, sensor modules able to detect analytes that arebreast cancer markers. The flexible gel-filled implant is fabricated byforming an exterior shell from a silicon elastomer using a mold. Theexterior shell is configured to be filled with a viscous material, suchas a gel. Methods and compositions to make elastomeric breast prosthesesthat can be filled with gel are described (see e.g., U.S. Pat. No.8,043,373 “All-Barrier Elastomeric Gel-Filled Breast Prosthesis,” toSchuessler and Powell, which is incorporated herein by reference). Forexample, the exterior or outer shell may be formed frompolydimethylsiloxane containing approximately 15 mole percentdiphenylsiloxane (polysiloxanes are available from NuSil Technology,Carpenteria, Calif.). A two-piece rotational mold with a liner may beused to cast the outer shell. A hemispherical seamless, breast implantshell with a wall thickness of approximately 0.456 mm and a basediameter of approximately 12 cm may be manufactured with a rotationalmold (see e.g., U.S. Pat. No. 8,043,373, Ibid.). The shell can be filledat a later time with silicone gel (see e.g., U.S. Pat. No. 8,043,373,Ibid.). Multiple sensor modules able to detect analytes that are breastcancer markers are fabricated on the surface of the implant shell tomonitor the tissue exudates and interstitial fluids surrounding theimplant.

Sensor modules are printed on the surface of the breast implant shell todetect multiple analytes and, therefore, different biomarkers associatedwith breast cancer. Long-lived sensor modules which signalelectronically when they encounter analytes are deposited on the implantshell surface by an ink jet printing process. Methods and materials tofabricate long-lived analyte sensor modules are described (see e.g.,U.S. Pat. No. 7,577,470, “Long Term Analyte Sensor Array” to Shah etal., and US Patent Application No. 2010/0276302, “Chemiresistor for Usein Conducting Electrolyte Solution,” to Raguse and Chow, which are eachincorporated herein by reference). For example chemiresistor sensorunits may be printed on the polysiloxane shell using an aerosol-jetprinter (see e.g., U.S. Pat. No. 7,485,345, “Apparatuses and Methods forMaskless Mesoscale Material Deposition,” to Renn et al. which isincorporated herein by reference). Initially, gold aerosols are printedto form parallel band electrodes that are approximately 3 mm long and 5μm wide separated by a gap of approximately 5 μm. Chemiresistor sensorunits are printed using dimethylamino pyridine (DMAP) coated goldnanoparticles (see e.g., U.S. Patent Appl. 2010/0276302, Ibid.) tocreate a circular nanoparticle film approximately 300 μm in diameterwhich coats a portion of both bands of the gold band electrodes. Next aligand containing a thiol group is added to the DMAP-gold particles tobind analyte. For example, the DMAP-gold nanoparticles are exposed tohexanethiol gas to yield a functional chemiresistor.

Additional electronic components of the sensor module can include: apotentiostat; a battery; a RFID tag; and integrated circuitry. All areprinted onto the polysiloxane shell. Methods and materials to printmetal traces, inductive coils, interdigitated capacitors, resistorterminations and antennas are described (see e.g., U.S. Pat. No.7,485,345, Ibid.). Additionally a battery is printed onto the shellattached to each sensor module using known methods and materials (seee.g., U.S. Pat. No. 7,129,166, “Method of Forming an Electronic Device,”to Speakman which is incorporated herein by reference). For example, abattery can be printed onto the polysiloxane shell by layering Li—Al toform the negative electrode, polyimide to form a containment well, LiBF₄as an electrolyte separator, and lastly a metallic positive electrode.The layered battery can be coated with acrylate to form a barrier layerover the battery.

A RFID unit that includes antennas and circuitry to receive and transmitradio frequency signals that identify each sensor module on the breastimplant is fabricated on the implant shell. The RFID unit can beconstructed by printing conductive ink (e.g., polymer with flecks ofsilver) to create circuitry. Conductive ink is used to print RFIDantennas and to connect electronic components on the device. Forexample, an integrated circuit defining the RFID circuitry for thedevice is printed on the substrate with conductive epoxy in connectionwith the conductive ink. The antenna can be a dipole antenna with acapacitor built in to store some of the electrical energy harvested fromincident radio waves. The device can have a transmit circuit and areceive circuit to control radio wave communications through theantenna, a power harvester circuit to provide power to the device and acontrol circuit. Encapsulating epoxy material is used to cover theintegrated circuit, the conductive ink and conductive epoxy. Methods andmaterials to construct RFID tags connected to sensors are described (seee.g.: U.S. Pat. No. 7,479,886, “Antenna Capacitance for Energy Storage,”to Burr; and U.S. Pat. No. 7,411,505, “Switch Status and RFID Tag,” toSmith et al., which are each incorporated herein by reference). The RFIDdevice with an antenna for transmitting signals to a RFID reader can beconstructed with circuitry able to send an identification signal thatincludes location information, and to transmit an alert when an analytethat is a breast marker is detected (see e.g., Sample et al., “Design ofan RFID-Based Battery-Free Programmable Sensing Platform,” IEEE Trans.Instr. Meas. 57: 2608-2615, (2008) which is incorporated herein byreference).

Sensor modules are printed over the surface of the implant shell todetect analytes that are breast cancer markers arising in breast tissuenear exterior surfaces of the implant. For example, a hemisphericalbreast implant shell with a base diameter of approximately 12 cm willhave a total surface area of approximately 300 cm², which can haveapproximately 50 to 100 sensor modules printed with approximately 3 cmto 6 cm between the midpoints of each sensor module and uniformlydistributed over the surface of the implant. The chemiresistor sensorunits are fabricated to detect different analytes, and, therefore,multiple breast cancer markers. Different thiol ligands and thiol ligandmixtures are used to functionalize the nanoparticle films to createdistinct chemiresistor sensor units responsive to different breastcancer markers. For example, chemiresistor sensor units containingDMAP-gold nanoparticle films are functionalized by exposure to differentligands (e.g., 1-hexanethiol and 4-mercaptophenol) and to mixtures ofthese ligands that modulate the sensor unit response to differentanalytes (see e.g., chemiresistor sensors responsive to the analytes,toluene and ethanol, in U.S. Patent Appl. 2010/0276302 Ibid.). Multiplechemiresistor sensor units functionalized with different thiol ligandsand ligand mixtures may be screened with breast cancer markers toidentify sensor units responsive to the breast cancer markers.Thiol-functionalized binding aptamers can be obtained from commercialsources such as Integrated DNA Technology, Inc. (Coralville, Iowa). Forexample, a panel of 7 different metabolites associated with breastcancer may be screened to identify responsive chemiresistor sensorunits. Increased levels of the metabolites formate, histidine, proline,choline, glutamic acid, N-acetyl-glycine, and3-hydroxy-2-methyl-butanoic acid are correlated with the recurrence ofbreast cancer (see e.g., Asiago et al., “Early Detection of RecurrentBreast Cancer Using Metabolite Profiling,” Cancer Research 70:8309-8318, 2010 which is incorporated herein by reference).

Sensor modules can contain replicate sets of different chemiresistorsensor units which respond to different breast cancer markers (see FIG.11). Moreover, the replicate sensor units can be protected with coversthat can be removed as needed to monitor breast cancer markers overseveral years. For example, sensor modules containing multiple sets ofsensor units for 7 breast cancer markers (see FIG. 11) may be coveredwith an analyte sensor membrane (e.g., a thin gold foil) that protectsthe sensors from exposure to interstitial fluid and cells. When a set ofsensor units becomes nonfunctional, i.e., no longer signals, it may bedeactivated and a new set of sensor units may be activated by disruptingthe protective membrane and engaging the circuitry to the new set ofsensor units. The protective membrane is disrupted by the application ofan electric current or potential which disrupts the gold foil andexposes the set of sensor units to the surrounding interstitial fluidand tissues (see e.g., U.S. Pat. No. 7,577,470 Ibid.). Replicate sets ofsensor units, each containing 7 different chemiresistor sensor unitsconfigured to detect analytes that are breast cancer markers, can besequentially exposed to monitor the regions surrounding the breastcancer implant over a period of approximately 5 years.

The breast implant with multiple sensor modules printed onto its surfaceis filled with an elastic silicone gel and treated with a coating toreduce encapsulation of the implant and to promote vascularization ofthe surrounding tissue. Following molding and printing of the breastimplant shell with multiple sensor arrays on the shell surface, asilicone gel is injected into the implant through an orifice at the baseof the implant. Methods and materials to inject the silicone gel and toseal the orifice with siloxane elastomer are described (see e.g., U.S.Pat. No. 8,043,373 Ibid.).

Finally, to prevent fibrous capsule formation and to promotevascularization around the breast implant, a semiporous membrane is usedto coat the implant. For example, a membrane of Gore® Teflon (availablefrom W. L. Gore & Associates, Inc., Newark, Del.) with a pore size ofapproximately 3 um is used to coat the breast implant and to promote avascularized interface with the implant and to prevent capsule formation(see e.g., U.S. Pat. No. 5,800,529 to Brauker et al., “CloseVascularization Implant Material,” which is incorporated herein byreference).

The breast implant system including the breast implant prosthesis withmultiple, distributed sensor modules and an external, remote deviceincluding a receiver is used to reconstruct the patient's breast and tomonitor tissue exudates and interstitial fluids for breast cancermarkers. The remote device can be a cell phone which is configured tosend signals to control the sensor units (e.g., activating specificsensor units distributed over the surface of the breast implant shell)and receive signals initiated by the sensor modules when changes inbreast cancer analytes are detected. The cell phone may alert thepatient and or the patient's physician when breast cancer analytes aredetected or sensor units become dysfunctional or the system is otherwisein need of attention.

Example 2 A Breast Implant System for Breast Augmentation IncludingSensor Modules with Attached RFID Units for Transmission of SensorModule Information

A patient undergoes breast augmentation surgery employing a breastimplant system that includes breast implant prostheses with sensormodules able to monitor for cancer biomarkers in tissue exudates andinterstitial fluids surrounding the breast implants. The breast implantsystem detects shed or secreted breast cancer analytes with a network ofsensor modules (see FIG. 2) distributed on the surface of the implant.The sensor modules signal wirelessly to an external, remote device wheninterrogated by the device, and the remote device alerts the patient andthe patient's medical team when analytes that are breast cancerbiomarkers are detected.

The breast implant prosthesis shell structure is fabricated as describedin Example 1. Sensor modules configured to detect breast cancer analytesof interest are fabricated containing electrochemical sensors withaptamer-based recognition elements. Methods to select and produceaptamers (i.e., oligonucleotides with high affinity binding to moleculartargets such as breast cancer antigens) are known (see e.g., U.S. Pat.No. 5,475,096, “Nucleic Acid Ligands,” to Gold, which is incorporatedherein by reference). The construction of electrochemical sensors usingmicrofabrication methods and employing aptamers to recognize specificbiomolecules has been described. See e.g.: U.S. Pat. No. 8,145,434,“Method and Apparatus for Forming a Homeostatic Loop Employing anAptamer Biosensor,” to Shachar et al.; Lee et al., “Aptamers asMolecular Recognition Elements for Electrical Nanobiosensors,” Anal.Bioanal. Chem. 390: 1023-1032, (2008); and U.S. Pat. No. 8,138,005“Method for Fabricating Novel High-Performance Field-Effect TransistorBiosensor Based on Conductive Polymer Nanomaterials Functionalized withAnti-VEGF Adapter,” to Jang et al. which are each incorporated herein byreference. For example, aptamers can be selected which bind with highaffinity and specificity to breast cancer biomarker proteins, such asthose produced by HER2 expressing (“HER-2+”) cells (see, e.g.: Thiel etal., “Delivery of Chemo-Sensitizing siRNAs to HER2+-Breast Cancer CellsUsing RNA Aptamers,” Nucleic Acids Research, doi:10.1093/nar/gks294,1-19 (2012) and the Supplementary Methods appendix thereof, includingthe aptamer sequences in Supplementary Table and International PatentApplication No. WO2011/142970, “HER2 Nucleic Acid Aptamers,” toGingrande et al., which are each incorporated herein by reference). Forexample, aptamers can be selected which bind with high affinity andspecificity to breast cancer biomarker proteins, such as those producedby HER3 expressing cells. For example, aptamers configured tospecifically bind to HER3 proteins expressed from breast cancer cellshave been described (see, e.g.: Chen et al., “Inhibition of HeregulinSignaling by an Aptamer that Preferentially Binds to the Oligomeric Formof Human Epidermal Growth Factor Receptor-3,” PNAS 100(16), 9226-9231(2003), which is incorporated herein by reference).

Each sensor unit (see FIG. 7) can be fabricated to include multipleelectrodes with different aptamers bound. For example, aptamers thatspecifically recognize HER2 proteins, HER3 proteins and VEGF (see: Thielet al., ibid; International Patent Application No. WO2011/142970, ibid.;Chen et al., ibid; and U.S. Pat. No. 8,138,005 to Jang et al., ibid,which are each incorporated by reference herein) can be immobilized ondifferent electrodes in the same sensor unit. The sensor modules cancontain multiple electrodes coated with capture reagents, i.e.,aptamers, to form capacitive plates. Aptamers can be attached to theelectrodes using a chemical linker, (e.g., succinic anhydride) whichfirst bonds to the electrodes using amino-sialanization and thencovalently couples with the aptamers during fabrication. The sensormodules include electronic components which form a capacitance detectorcircuit. The capacitance detector circuit can include: an amplifierbuffer, a current to voltage amplifier, resistors, and integrationcircuits. Binding of biomolecules, e.g., proteins, to the immobilizedaptamers changes the impedance at the electrode-solution interface, andchanges in impedance can be correlated with the amount of proteinanalyte bound to the immobilized aptamers (see e.g., U.S. Pat. No.8,145,434, Ibid.).

The sensor modules (see FIG. 7) configured to detect breast canceranalytes are machined on silicon chips and each include transmissionunits with RFID units and related circuitry. Fabrication of RFID deviceswith integrated sensors as microchips approximately 2 cm×2 cm has beendescribed (see e.g., Sample et al., “Design of an RFID-BasedBattery-Free Programmable Sensing Platform,” IEEE Trans. Instr. Meas.57: 2608-2615, (2008) which is incorporated herein by reference). Forexample, sensors requiring less than approximately 500 μA of surfacespace can be integrated and empowered with an RFID device. Each RFIDunit is configured to provide wireless communication with a remotedevice including an external RFID reader. Each RFID unit is configuredto harvest power from a signal transmitted from the remote device toempower the sensor modules (i.e., a “passive RFID”). Each RFID unit isconfigured to transmit a signal identifying the specific RFID unit, andby extension, the attached sensor module. Each RFID unit includes atleast one antenna and associated circuitry to receive and transmit radiofrequency signals. Methods and materials to construct RFID units withantennas, transmitters, and power harvesters are described (see e.g:U.S. Pat. No. 7,479,886, “Antenna Capacitance for Energy Storage,” toBurr; and U.S. Pat. No. 7,411,505, “Switch Status and RFID Tag,” toSmith et al., which are each incorporated herein by reference). Theantenna can be a dipole antenna with a capacitor built in to store someof the electrical energy harvested from incident radio waves. The devicecan include a transmit circuit and a receive circuit to control radiowave communications through the antenna, a power harvester circuit toprovide power to the device and a control circuit. The RFID unit can beconstructed with circuitry to send an identification signal for thatunit, and to transmit an alert when the sensor module detects theanalyte.

The sensor modules with aptamer-based sensors and RFID devices areattached to the shell of the breast implant in a uniformly distributednetwork. The sensor units can be attached, for example, using anadhesive. For example, a hemispherical breast implant shell with adiameter of approximately 12 cm will have a total surface area ofapproximately 300 cm² and can include approximately 50 to 100 sensorunits attached approximately 3 to 6 cm apart and uniformly distributedover the surface of the implant.

Sensor modules contain multiple, replicate aptamer-based sensor unitsable to detect a set of breast cancer markers. For example, each sensormodule can include 56 replicate sensor units with each sensor unitdetecting 3 different cancer analytes. See FIG. 11. Sensor modulescontaining multiple sensor units have been described (see e.g., U.S.Pat. No. 7,577,470, Ibid). The 56 sensor units present on each sensormodule can be protected with covers that can be individually removed asneeded to monitor breast cancer antigens over several years. Forexample, the individual sensor units can be covered with analyte sensormembranes (e.g., thin gold foil) that protect the sensors frominterstitial fluid, cells, and biofouling. When a new sensor unit isneeded on a sensor module, the protective membrane over one sensor unitis removed by the application of an electric current which disrupts thegold foil cover and exposes the new sensor unit to surroundinginterstitial fluid and tissues (see e.g., U.S. Pat. No. 7,577,470Ibid.). Replicate sensor units for breast cancer markers can besequentially exposed in order to monitor the regions surrounding thebreast cancer implant over a period of approximately 5 years. If asensor becomes nonfunctional, i.e., no longer signals, a signal can bereceived from a remote device that initiates deactivation of thenonfunctional sensor unit and disruption of the protective membrane toexpose a new sensor unit as well as engaging circuitry to activate thenew sensor unit.

As described above in FIG. 1, the breast implant shell is filled with anelastic silicone gel and treated with a coating to reduce encapsulationof the implant and to promote vascularization of the surrounding tissue.Following molding of the breast implant shell and attachment of multiplesensor modules on the shell surface with an appropriate adhesive, asilicone gel is injected into the implant through an orifice at the baseof the implant. Methods and materials to inject the silicone gel and toseal the orifice with siloxane elastomer are described (see e.g., U.S.Pat. No. 8,043,373 Ibid.).

The breast implant system including the breast implant prostheses withmultiple sensor modules is used to aesthetically augment theindividual's breasts and also used in combination with a remote deviceincluding an external RFID reader to functionally monitor tissueexudates and interstitial fluids for breast cancer analytes. The remotedevice that includes an external RFID reader can be part of a cellphone. The remote device that includes an external RFID reader can sendsignals to control the sensor modules (e.g., activating specific sensorunits distributed over the surface of the breast implant shell) andreceive signals from the sensor modules when changes in breast cancermarkers are detected. The cell phone can alert the patient and thepatient's physician when analytes that are breast cancer markers aredetected or when sensor modules become dysfunctional or need attention.

Example 3 A Breast Implant System with Directed Flow Configured forBreast Reconstruction and Monitoring of Interstitial Fluids for Analytesthat are Breast Cancer Biomarkers

A patient with breast cancer undergoes a total mastectomy of theaffected breast, and after suitable medical treatment the breast isreconstructed with a breast implant system. The breast implant systemincludes a gel-filled breast implant prostheses including multiplelong-lived sensor modules configured to monitor the tissues surroundingthe implant for any new or recurrent breast cancers that may arise. Thebreast implant includes an enveloping membrane including microchannelsconfigured to direct interstitial fluids surrounding the implant topositions adjacent to sensor modules on the implant shell. The longlived sensor modules are configured to detect analytes that are breastcancer markers. The long lived sensor modules each include a powersource, a transmitter, an identification code and a unique identifier.The implant system also includes a remote device with an externalreceiver configured to receive transmissions from the sensor modules andto alert the patient and medical personnel if breast cancer markers aredetected.

The breast implant prosthesis shell with attached sensor modules isfabricated as described in Example 1. Multiple analyte sensor modulesare printed on the surface of the breast implant shell and configured todetect analytes associated with breast cancer.

Additional electronic components of the sensor module can include: apotentiostat; a battery; a RFID unit; and integrated circuitry. Allcomponents are printed onto the polysiloxane shell of the breastimplant. Methods and materials to print metal traces, inductive coils,interdigitated capacitors, resistor terminations and antennas aredescribed (see e.g., U.S. Pat. No. 7,485,345 Ibid.). Additionally, atleast one battery is printed onto the shell and attached to each sensormodule using known methods and materials (see e.g., U.S. Pat. No.7,129,166, “Method of Forming an Electronic Device,” to Speakman whichis incorporated herein by reference). See also Example 1.

Following molding and printing of the breast implant shell with multiplesensor modules on the shell surface, a silicone gel is injected into theimplant through an orifice at the base of the implant. Methods andmaterials to inject the silicone gel and to seal the orifice withsiloxane elastomer are described (see e.g., U.S. Pat. No. 8,043,373Ibid.).

A fluid transport film is fabricated to correspond to the externalsurface of the breast implant and configured to transport interstitialfluid from the periphery of the implant to the sensor modules on theimplant shell. Fluid transport films constructed from polyolefins bymolding microchannels into a polymer film are described. See, forexample, U.S. Pat. No. 6,420,622 “Medical Article Having Fluid ControlFilm,” to Johnston et al., which is incorporated herein by reference.For example, a polymer film of polypropylene is cast with replicatedparallel microchannels that are rectilinear and have a width less than1500 μm and a depth of approximately 100-1000 μm. Interstitial fluidsare wicked through microchannels of the fluid transport film, collectedin a manifold and directed via a connector to proximal sensor modules.Fluid transport films with microchannels, a manifold, a connector and avacuum source are described (see e.g., U.S. Pat. No. 6,420,622, Ibid.).A fluid transport film is fabricated with microchannels to collectinterstitial fluid from all surfaces of the implant shell and to deliverthe fluids to sensor modules proximal to the collection sites. The fluidtransport film is substantially the same shape as the implant,configured to correspond to the outer surface of the shell with a gapbetween the film and the outer surface of the shell. The fluid transportfilm is positioned around the outer surface of the shell. At least onetether may be fabricated to connect the film and the outer surface ofthe shell, the tether(s) adhered to both the film and the outer surfaceof the shell with a suitable adhesive.

Example 4 A Breast Implant System for Breast Augmentation Configured toPermit Magnetic Resonance Imaging

A patient undergoes breast augmentation surgery employing a breastimplant system that includes breast implant prostheses with sensormodules configured to monitor for cancer biomarkers in tissue exudatesand interstitial fluids surrounding the breast implants. The breastimplant system detects shed or secreted breast cancer analytes with anetwork of sensor modules (see, e.g. FIG. 2) distributed on the surfaceof the implant. The sensor modules are configured to signal wirelesslyto an external receiver when interrogated by an external deviceincluding a reader. The external device including the receiver can sendalerts to the patient and to the patient's physician when breast canceranalytes are detected.

The breast implant prosthesis is a gel-filled hemispherical orcrescent-shaped implant including a shell. The implant includes sensormodules attached to the surface of the shell. The sensor modules areconfigured to detect analytes that are breast cancer markers. SeeExamples 1-3.

Sensor modules are fabricated containing antibody-based electrochemicalsensor units, with removable covers, as described (see, e.g. U.S. Pat.No. 7,577,470, “Long Term Analyte Sensor Array,” to Shah et al., whichis incorporated herein by reference). Antibodies directed to specificrecognition of breast cancer analytes are commercially available. Forexample, multiple antibodies directed to the breast cancer analyte HER-2(also known as ErbB2) are available from R&D Systems, Minneapolis Minn.For example, multiple antibodies directed to the breast cancer analytematrix metalloproteinase-2, or “MMP-2,” are available from NovusBiologicals, Littleton, Colo. For example, antibodies directed to thebreast cancer analyte CA 15-3 are available from Lee Biosolutions, St.Louis, Mo. Each sensor module includes: at least one sensor unitconfigured to detect HER-2 with a HER-2 specific antibody; at least onesensor unit configured to detect MMP-2 with a MMP-2 specific antibody;and at least one sensor unit configured to detect CA 15-3 with a CA 15-3specific antibody. Each sensor module is attached to a transmission unitconfigured to receive signals from the sensor units when analytes aredetected, and to send a signal to a remote device external to the bodyincluding the implant (see, e.g. U.S. Pat. No. 7,577,470, ibid). Thesensor modules configured to detect breast cancer antigens are machinedon silicon chips, and constructed with non-ferromagnetic materials(i.e., paramagnetic or diamagnetic) and/or metal alloys that areminimally affected by an external magnetic field in order to becompatible with magnetic resonance imaging (MRI).

A transmission unit is fabricated to attach to each sensor module. Eachtransmission unit includes at least one antenna and circuitry to receiveand transmit radio frequency signals. A transmission unit can beconfigured to send and receive signals in the radio frequency spectrumand including a unique identifier, i.e. to be a “RFID unit.” Eachtransmission unit includes a unique identifier to identify informationfrom a particular sensor module on the breast implant. Methods andmaterials to construct transmission units with antennas, transmitters,and power harvesters are described (see e.g: U.S. Pat. No. 7,479,886,“Antenna Capacitance for Energy Storage,” to Burr; and U.S. Pat. No.7,411,505, “Switch Status and RFID Tag,” to Smith et al., which are eachincorporated herein by reference). Each transmission unit is fabricatedfrom MRI-compatible materials. Transmission units constructed fromnon-ferromagnetic materials which are compatible with MRI studies aredescribed (see e.g., U.S. Patent Application No. 2011/0077736, “BreastImplant System Including Bio-Medical Units,” to Rofougaran and U.S.Patent Application No. 2007/0106332, “MRI Compatible ImplantedElectronic Medical Device,” to Denker et al. which are each incorporatedherein by reference).

The sensor modules are attached to the shell of the breast implant in auniformly distributed network. For example, a hemispherical breastimplant shell with a diameter of approximately 12 cm will have a totalsurface area of approximately 300 cm² and can include approximately 50to 100 sensor modules attached with their midpoints approximately 3 to 6cm apart and uniformly distributed over the surface of the implant. Thesensor modules and transmission units are attached using suitableadhesive.

The breast implant shell is filled with an elastic silicone gel.Following molding of the breast implant shell and attachment of multiplesensor modules on the shell surface, a silicone gel is injected into theimplant through an orifice at the base of the implant. Methods andmaterials to inject the silicone gel and to seal the orifice withsiloxane elastomer are described (see e.g., U.S. Pat. No. 8,043,373Ibid.).

Sensor modules can contain multiple, replicate antibody-based sensorunits which detect a set of breast cancer markers. For example, eachsensor module can include approximately 70 replicate sensor units witheach sensor unit detecting 3 different cancer antibodies (e.g., HER-2,MMP-2 and CA 15-3). See FIG. 11. Sensor modules containing multiplesensor units have been described (see e.g., U.S. Pat. No. 7,577,470,Ibid.). The 70 sensor units present in each sensor module can beprotected with covers that can be individually removed as needed tomonitor breast cancer antigens over several years. For example, theindividual sensor units can be covered with membranes (e.g., thin goldfoil) that protect the sensors from interstitial fluid, cells, andbiofouling. When a new sensor unit is needed on a sensor module, theprotective membrane over one sensor unit is removed by the applicationof an electric current which disrupts the gold foil cover and exposesthe new sensor unit to surrounding interstitial fluid and tissues (seee.g., U.S. Pat. No. 7,577,470, Ibid.). Replicate sensor units configuredto detect the same breast cancer analyte can be sequentially exposed tomonitor the regions surrounding the breast cancer implant over a periodof approximately 5 years. If a sensor becomes nonfunctional, i.e., nolonger signals, it can be deactivated by wireless signaling from aremote device. A new sensor unit can be activated by disrupting itsprotective membrane and engaging circuitry to the new sensor unit.

The breast implant system including the breast implant prostheses withmultiple sensor modules is used to augment the patient's breasts. Aftersurgery, an external device is used monitor the sensor modules detectionof analytes that are breast cancer markers in tissue fluids. Theexternal device can be configured to transmit radiowaves that signal thesensor modules and provide a source of power. External devices tocommunicate with sensor modules are described (see e.g., U.S. PatentAppl. No. 2011/0077736, Ibid.). The external device can be a cell phoneconfigured to receive signals from the transmission units when breastcancer analytes are detected. For example, an external device installedin the patient's home may interrogate and empower the sensor modules onthe breast implants daily when the patient arrives home. The externaldevice can be configured to control the sensor modules, such as bytriggering activation of specific sensor units distributed over thesurface of the breast implant shell through removal of a specific coveror set of covers. The external device can alert the patient and thepatient's physician when breast cancer markers are detected, or sensormodules become dysfunctional, or the system otherwise needs attention.

Example 5 A Breast Implant System with Compartments Containing LocalizedSensor Modules Configured to Detect Breast Cancer Analytes

A patient has a total reconstruction of the breast employing a breastimplant system. The breast implant system includes a gel-filled breastimplant prosthesis including a shell (see Example 1, above). The breastimplant includes external projections forming a series of compartmentson the surface of the implant shell. The external projections areconfigured like a plurality of membranes projecting at substantiallyright angles from the exterior surface of the implant shell, creating aseries of compartments on the shell surface. Breast implant prosthesiswith membranes attached to the surface are described. See, e.g. U.S.Pat. No. 3,559,214, “Compound Prosthesis,” to Pangman. The projectionsattached to the instant embodiment are adjacent to the outer surface ofthe shell. The projections can be fabricated from a similar material asthe shell, and attached to the shell at approximately right angles tothe shell surface. The projections are substantially planar sheets ofsoft, bio-compatible material attached to the exterior surface of theshell with a suitable adhesive. The projections form a series ofcompartments adjacent to the surface. Each compartment has a depthapproximately equivalent to the height of the projections forming thecompartment. The projections are approximately 2 to approximately 10 mmin height, as measured from the surface of the shell to the distal edgeof the projection.

For example, FIG. 12 illustrates a breast implant 140 including a shell145. The view illustrated in FIG. 12 is an external, frontal view of abreast implant 140 ex-vivo. The exterior of the shell 145 includes aplurality of projections 1400 extending at substantially right anglesfrom the face of the external surface of the shell 145. The projections1400 are substantially planar, sheet-like projections. Since the breastimplant 140 is depicted in a frontal view, the projections 1400 aredepicted as lines over the surface of the shell 145. The projections1400 continue beyond the surface of the shell 145, which is illustrated1410. The plurality of projections 1400 form a series of compartments1420 on the surface of the shell 145. Each of the compartments 1420includes sensor modules 150. In the illustration shown in FIG. 14, eachcompartment 1420 includes two sensor modules 150. The compartments 1420are substantially rectangular with their long axis orientedapproximately vertically relative to the expected position of the breastimplant 140 in vivo. This position facilitates gravity enhancing theflow of interstitial fluid from the top to the bottom through eachcompartment 1420 when the breast implant 140 is in situ (see dottedarrows).

Each compartment includes at least one long-lived sensor moduleconfigured to monitor the tissues surrounding the implant, morespecifically those adjacent to the compartment, for analytes indicatingany new or recurrent breast cancers that may arise. Each compartmentincludes at least one transmission unit attached to a sensor module. SeeExample 2 for a description of the sensor modules and attachedtransmission units. Sensor modules and transmission units are attachedto the shell of the breast implant within the compartments andconfigured to monitor the interstitial fluids entering each compartment.For example, a hemispherical breast implant shell with a diameter ofapproximately 12 cm and a total surface area of approximately 300 cm²can include approximately 15 compartments with each circumscribingapproximately 20 cm². Each compartment can contain 1-3 sensor modules tomonitor the region proximal to the compartment. The implant can includea total of approximately 30-45 sensor modules to monitor interstitialfluids from tissues surrounding the breast implant. Each sensor moduleand transmission unit is attached to the surface of the shell with asuitable adhesive in a compartment region formed between theprojections. See FIG. 12.

Following molding of the breast implant shell with exterior partitionsand attachment of multiple sensor modules on the shell surface, asilicone gel is injected into the implant through an orifice at the baseof the implant. Methods and materials to inject the silicone gel and toseal the orifice with siloxane elastomer are described (see e.g., U.S.Pat. No. 8,043,373 Ibid.).

The breast implant system including the breast implant prosthesis withcompartments containing sensor modules and transmission units is used toreconstruct the patient's breast. Over time, the implant and anexternal, remote device is used to monitor tissue exudates andinterstitial fluids for analytes that are breast cancer biomarkers. Theimplant system includes an external, remote device with a receiveroperable to receive transmissions from the transmission units and adisplay that can be activated to alert the patient and medical personnelif the analytes are detected. The external, remote device can be a cellphone configured to receive signals from the transmission units. Theexternal, remote device can be configured to send signals that controlthe sensor modules, such as by triggering activation of specific sensorunits distributed over the surface of the breast implant shell throughremoval of a specific cover or set of covers. The external, remotedevice can alert the patient and the patient's physician when breastcancer analytes are detected, or sensor modules become dysfunctional, orthe system needs attention.

Example 6 A Breast Implant System with Compartments Containing LocalizedSensor Modules Configured to Permit Magnetic Resonance Imaging

A patient undergoes breast augmentation surgery employing a breastimplant system. The breast implants include projections formingcompartments, as described in Example 5. Attached to the surface of theshell within each compartment is at least one sensor module and anattached transmission unit configured to harvest operating power fromincoming RF signals. See Example 4. The transmission units each includean identification code specific to that unit. The transmission units areconfigured to signal wirelessly to an external receiver wheninterrogated by remote device. The remote device includes a display toalert the patient and the patient's physician when breast canceranalytes are detected.

The breast implant system is fabricated to be MRI-compatible. The breastimplant shell, projections and interior viscous material are selected tobe MRI-compatible. In addition, each sensor module and attachedtransmission unit is fabricated from MRI-compatible materials. See e.g.,U.S. Patent Application No. 2011/0077736, “Breast Implant SystemIncluding Bio-Medical Units,” to Rofougaran and U.S. Patent ApplicationNo. 2007/0106332, “MRI Compatible Implanted Electronic Medical Device,”to Denker et al. which are each incorporated herein by reference. Forexample, the implanted system, including sensor units and transmissionunits, can be fabricated from non-ferromagnetic materials. For example,the electrical connections of the sensor modules and attachedtransmission units can be made with silica or plastic based fibers.

Following molding of the breast implant shell with exterior partitionsand attachment of multiple sensor modules on the shell surface, asilicone gel is injected into the implant through an orifice at the baseof the implant. Methods and materials to inject the silicone gel and toseal the orifice with siloxane elastomer are described (see e.g., U.S.Pat. No. 8,043,373 Ibid.).

The breast implant shell is encased in at least one fluid transport filmto enclose the compartments on their outer sides, distal to the surfaceof the shell. The film is configured to promote fluid flow into thecompartments from the adjacent tissue region. Following molding of thebreast implant shell with exterior projections and attachment ofmultiple sensor modules and transmission units on the shell surface, afluid transport film is fabricated to enclose the compartments on thebreast implant shell. The fluid transport film is configured totransport interstitial fluid into the compartments and into proximitywith the sensor modules. Fluid transport films constructed frompolyolefins by molding microchannels into a polymer film are described(see e.g, U.S. Pat. No. 6,420,622 “Medical Article Having Fluid ControlFilm,” to Johnston et al., which is incorporated herein by reference).For example, a polymer film of polypropylene can be cast with replicatedparallel microchannels which are rectilinear with a width less than 1500μm and a depth of approximately 100-1000 μm. Interstitial fluids arewicked through microchannels of the fluid transport film, collected in amanifold and directed via a connector to proximal sensor modules. Thefluid transport film is substantially the same shape as the implant,configured to correspond to the outer surface of the shell with a gapbetween the film and the outer surface of the shell. The fluid transportfilm is positioned around the outer surface of the shell. At least onetether may be fabricated to connect the film and the outer surface ofthe shell, the tether(s) adhered to both the film and the outer surfaceof the shell with a suitable adhesive. The implant can also be envelopedwith coatings to reduce encapsulation of the implant and to promotevascularization of the surrounding tissue (see above Examples).

Example 7 A Breast Implant System Harvesting Optical Power

A patient with breast cancer undergoes a total mastectomy of theaffected breast, and after suitable medical treatment the breast isreconstructed with a breast implant system. The breast implant systemincludes a gel-filled breast implant and multiple attached long-livedsensor modules configured to monitor the tissues surrounding the implantfor any new or recurrent breast cancers that may arise. See Example 2.The long lived sensor modules can detect analytes that are breast cancermarkers and report the detection via attached transmission units. Thelong lived sensor modules are each operably attached to an optical powercollector affixed to the shell. An optical power converter attached toeach sensor module converts harvested optical power into electricalpower for the sensor module and attached transmission unit. The implantsystem also includes a remote device with an external receiverconfigured to receive transmissions from the implant and to alert thepatient and medical personnel if breast cancer analytes are detected.

Multiple analyte sensor modules are attached to the surface of thebreast implant shell and configured to detect analytes associated withbreast cancer. The implant also includes at least one optical powercollector configured to harvest optical energy and a series of opticalfibers connecting the optical power collector to optical powerconverters attached to each sensor module. The breast implant prosthesisshell with attached sensor modules and attached transmission units isfabricated as described in Example 2, with the exception that each ofthe attached sensor modules and attached transmission units alsoincludes an attached optical power converter configured to convert thetransmitted optical power into electrical energy to power the sensormodules and attached transmission units. See e.g.: U.S. Patent Appl.2011/0044694, “Systems and Methods for Optically Powering Transducersand Related Transducers,” to Scherer et al.; US Patent Application No.2010/0070003, “Systems configured to power at least one device disposedin a living subject, and related apparatuses and methods,” to Hyde etal.; and Ayazian et al., “Delivering Optical Power to SubcutaneousImplanted Devices,” Conf Proc. IEEE Eng. Med. Biol. Soc. 2011: 2874-2877(2011), which are each incorporated herein by reference. Each opticalpower converter is configured to receive optical power from an opticalpower collector through an optic fiber attached to both the opticalpower collector and the power converter.

Sensor modules are empowered by an optical power converter that supplieselectric current to the sensor module. Optically powered transducers andconverters suitable for medical implants have been described (see e.g.:U.S. Patent Appl. 2011/0044694, “Systems and Methods for OpticallyPowering Transducers and Related Transducers,” to Scherer et al.; USPatent Application No. 2010/0070003, “Systems configured to power atleast one device disposed in a living subject, and related apparatusesand methods,” to Hyde et al.; and Ayazian et al., “Delivering OpticalPower to Subcutaneous Implanted Devices,” Conf. Proc. IEEE Eng. Med.Biol. Soc. 2011: 2874-2877 (2011), which are each incorporated herein byreference). For example, a photovoltaic collector and electroniccircuitry can be fabricated using a standard CMOS (Complementarymetal-oxide-semiconductor) process in a silicon foundry. A photovoltaiccollector irradiated with 10 mW/cm² of light input power yieldsapproximately 3.1 mW/cm² power output, i.e., an efficiency of about 31%.The optical power collector is attached to an outer surface of theimplant shell with suitable adhesive. The optical power collector(s) areattached to an outer surface of the implant shell at a location whereminimal tissue is expected to be positioned between the optical powercollector and the exterior skin surface of the patient. For example, theoptical power collector is attached to an outer surface of the implantshell at a location expected to correspond with the front region of thepatient's breast.

During medical exams, the optical power collectors are irradiated by anoptical reader that generates optical energy with a near-IRsemiconductor laser using a wavelength between approximately 680 nm and980 nm. An external optical reader with a near IR laser can provideoptical energy to the implant optical power collectors through as muchas several centimeters of tissue. The optical reader, an externalcomponent of the breast implant system, can be periodically utilized toempower the sensor modules and attached transmission units, such asduring medical visits, to monitor the breast implant for the potentialdetection of breast cancer analytes.

All of the above U.S. patents, U.S. patent application publications,U.S. patent applications, foreign patents, foreign patent applicationsand non-patent publications referred to in this specification and/orlisted in any Application Data Sheet, are incorporated herein byreference, to the extent not inconsistent herewith.

With respect to the appended claims, the recited operations therein maygenerally be performed in any order. Also, although various operationalflows are presented in a sequence(s), it should be understood that thevarious operations may be performed in other orders than those which areillustrated, or may be performed concurrently. Examples of suchalternate orderings may include overlapping, interleaved, interrupted,reordered, incremental, preparatory, supplemental, simultaneous,reverse, or other variant orderings, unless context dictates otherwise.Furthermore, terms like “responsive to,” “related to,” or otherpast-tense adjectives are generally not intended to exclude suchvariants, unless context dictates otherwise.

While various aspects and embodiments have been disclosed herein, otheraspects and embodiments will be apparent to those skilled in the art.The various aspects and embodiments disclosed herein are for purposes ofillustration and are not intended to be limiting, with the true scopeand spirit being indicated by the following claims.

What is claimed is: 1-108. (canceled)
 109. A method of monitoringinformation from a breast implant, comprising: receiving firstinformation from a first sensor module attached to a shell of a breastimplant within an individual, wherein the first information includes afirst unique sensor module identifier and sensor data from the firstsensor module; receiving second information from a second sensor moduleattached to the shell of the breast implant within the individual,wherein the second information includes a second unique sensor moduleidentifier and the sensor data from the second sensor module; forming aninitial record from the first information and the second formation;calculating deviation limits regarding the initial record; settingdeviation parameters based on the deviation limits and a predeterminedset of standards; saving the initial record and the deviation parametersin a memory in a computing device; receiving third information from thefirst sensor module attached to the shell of the breast implant withinthe individual, wherein the third information includes the first uniquesensor module identifier and the sensor data from the first sensormodule; receiving fourth information from the second sensor moduleattached to the shell of the breast implant within the individual,wherein the fourth information includes the second unique sensor moduleidentifier and the sensor data from the second sensor module; updatingthe initial record with the third information and the fourthinformation; saving the updated record in memory in the computingdevice; comparing the updated record to the initial record and to thedeviation parameters; and indicating if the updated record is within thedeviation parameters of the initial record.
 110. The method of claim109, comprising: receiving fifth information from the first sensormodule attached to the shell of the breast implant within theindividual, wherein the fifth information includes the first uniquesensor module identifier and the sensor data from the first sensormodule; receiving sixth information from the second sensor moduleattached to the shell of the breast implant within the individual,wherein the sixth information includes the second unique sensor moduleidentifier and the sensor data from the second sensor module; updatingthe initial record with the fifth information and the sixth information;saving the updated record in the memory in the computing device;comparing the updated record to the initial record and to the deviationparameters; indicating if the updated record is within the deviationparameters of the initial record.
 111. A method of monitoringinformation from a breast implant, comprising: sending a signal from atransmission unit attached to one or more sensor modules attached to abreast implant in vivo, wherein the signal contains informationregarding the detection of one or more biological analytes by the one ormore sensor modules.
 112. A method of monitoring information from abreast implant, comprising: directing, from an ex-vivo device, anon-electrical power source to a breast implant in-vivo; sending, from aremote device, a query signal to at least one transmission unit attachedto the breast implant in vivo, the at least one transmission unitattached to one or more sensor modules configured to detect biologicalanalytes in fluid from biological tissue; receiving, from a remotedevice, a response signal from the at least one transmission unitattached to the breast implant, the response signal includinginformation from the one or more sensor modules; processing, in acomputing device, the response signal to identify information from theone or more sensor modules; and identifying, for each of the one or moresensor modules, a detection result and a unique identifier.
 113. Themethod of claim 112, wherein the detection result for each of the one ormore sensor modules includes a positive result, a negative result, or anull result.
 114. The method of claim 112, comprising: initiating adisplay of the detection result and the unique identifier for at leastone of the sensor modules.
 115. The method of claim 112, comprising:initiating a graphic display of the breast implant, the graphic displayincluding a position for each of the sensor modules and the detectionresult for at least one of the sensor modules.
 116. A method ofmonitoring information from a breast implant, comprising: directing,from an ex-vivo device, a non-electrical power source to a breastimplant in vivo; sending a signal from at least one transmission unitattached to the breast implant in vivo, the signal including informationregarding one or more sensor modules configured to detect biologicalanalytes in fluid from biological tissue, the at least one transmissionunit attached to the one or more sensor modules; receiving, at a remotedevice, the signal from the at least one transmission unit attached tothe breast implant; processing, in a computing device, the signal toidentify information from the one or more sensor modules; andidentifying, for each of the one or more sensor modules, a detectionresult and a unique identifier.
 117. The method of claim 116, whereinthe detection result for each of the one or more sensor modules includesa positive result, a negative result, or a null result.
 118. The methodof claim 116, comprising: initiating a display of the detection resultand the unique identifier for at least one of the sensor modules. 119.The method of claim 116, comprising: initiating a graphic display of thebreast implant, the graphic display including a position for each of thesensor modules and the detection result for at least one of the sensormodules.
 120. A breast implant comprising: a shell configured to besubstantially filled with a viscous material, the shell including abarrier layer with a plurality of apertures, the plurality of apertureseach including a surface configured to reversibly mate with a region ofan outer surface of a sensor module; a plurality of projectionsincluding a first end extending from an external surface of the shell,the projections forming a plurality of compartments adjacent to theexternal surface of the shell; at least one fluid-permeable coverattached to the plurality of projections at a second end of eachprojection, the cover completely enveloping the shell and the pluralityof projections; and a plurality of sensor modules attached to the shellwith the region of an outer surface of each of the sensor modules matedto the surface of one of the plurality of apertures in the barrierlayer, each of the sensor modules positioned within one of the pluralityof compartments, wherein each of the plurality of sensor modules isconfigured to utilize energy transmitted from an external source. 121.The breast implant of claim 120, wherein the plurality of compartmentsare substantially sealed from each other.
 122. The breast implant ofclaim 120, wherein the plurality of sensor modules attached to the shellcomprise: at least one sensor module configured to detect at least twoanalytes in the fluid adjacent to the shell, wherein the at least twoanalytes are of different types.
 123. The breast implant of claim 120,wherein the plurality of sensor modules attached to the shell comprise:at least two sensor units in each of the plurality of sensor modules.124. The breast implant of claim 120, wherein the plurality of sensormodules attached to the shell comprise: a plurality of reservoirs, eachof the reservoirs including a removable cover.
 125. A breast implantcomprising: a shell configured to be substantially filled with a viscousmaterial, the shell including a plurality of cavities in a surface ofthe shell, the plurality of cavities each including a surface configuredto reversibly mate with a region of an outer surface of a sensor module;a plurality of projections including a first end extending from anexternal surface of the shell, the projections forming a plurality ofcompartments adjacent to the external surface of the shell; at least onefluid-permeable cover attached to the plurality of projections at asecond end of each projection, the cover completely enveloping the shelland the plurality of projections; and a plurality of sensor modulesattached to the shell with the region of an outer surface of each of thesensor modules mated to the surface of one of the plurality of cavities,each of the sensor modules positioned within one of the plurality ofcompartments, wherein each of the plurality of sensor modules isconfigured to utilize energy transmitted from an external source. 126.The breast implant of claim 125, wherein the plurality of compartmentsare substantially sealed from each other.
 127. The breast implant ofclaim 125, wherein the plurality of sensor modules attached to the shellcomprise: at least one sensor module configured to detect at least twoanalytes in the fluid adjacent to the shell, wherein the at least twoanalytes are of different types.
 128. The breast implant of claim 125,wherein the plurality of sensor modules attached to the shell comprise:at least two sensor units in each of the plurality of sensor modules.129. The breast implant of claim 125, wherein the plurality of sensormodules attached to the shell comprise: a plurality of reservoirs, eachof the reservoirs including a removable cover.